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id="toc-Cells_and_tissues_expressing_HCA2" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Cells_and_tissues_expressing_HCA2"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Cells and tissues expressing HCA<sub>2</sub></span> </div> </a> <ul id="toc-Cells_and_tissues_expressing_HCA2-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-HCA2_activating_agents" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#HCA2_activating_agents"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>HCA<sub>2</sub> activating agents</span> </div> </a> <ul id="toc-HCA2_activating_agents-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-HCA2's_function_in_lipolysis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#HCA2's_function_in_lipolysis"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>HCA<sub>2</sub>'s function in lipolysis</span> </div> </a> <ul id="toc-HCA2's_function_in_lipolysis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-HCA2's_functions_in_various_diseases" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#HCA2's_functions_in_various_diseases"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>HCA<sub>2</sub>'s functions in various diseases</span> </div> </a> <button aria-controls="toc-HCA2's_functions_in_various_diseases-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle HCA<sub>2</sub>'s functions in various diseases subsection</span> </button> <ul id="toc-HCA2's_functions_in_various_diseases-sublist" class="vector-toc-list"> <li id="toc-Atherosclerosis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Atherosclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.1</span> <span>Atherosclerosis</span> </div> </a> <ul id="toc-Atherosclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Stroke" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Stroke"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.2</span> <span>Stroke</span> </div> </a> <ul id="toc-Stroke-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Alzheimer's_disease" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Alzheimer's_disease"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.3</span> <span>Alzheimer's disease</span> </div> </a> <ul id="toc-Alzheimer's_disease-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Parkinson's_disease" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Parkinson's_disease"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.4</span> <span>Parkinson's disease</span> </div> </a> <ul id="toc-Parkinson's_disease-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Multiple_sclerosis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Multiple_sclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.5</span> <span>Multiple sclerosis</span> </div> </a> <ul id="toc-Multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Pathological_pain" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Pathological_pain"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.6</span> <span>Pathological pain</span> </div> </a> <ul id="toc-Pathological_pain-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Mastitis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Mastitis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.7</span> <span>Mastitis</span> </div> </a> <ul id="toc-Mastitis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Alcoholic_hepatitis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Alcoholic_hepatitis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.8</span> <span>Alcoholic hepatitis</span> </div> </a> <ul id="toc-Alcoholic_hepatitis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Inflammatory_bowel_disease_and_colon_cancer" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Inflammatory_bowel_disease_and_colon_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.9</span> <span>Inflammatory bowel disease and colon cancer</span> </div> </a> <ul id="toc-Inflammatory_bowel_disease_and_colon_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Other_diseases" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other_diseases"> <div class="vector-toc-text"> <span class="vector-toc-numb">5.10</span> <span>Other diseases</span> </div> </a> <ul id="toc-Other_diseases-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" 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</div> </nav> <nav class="vector-appearance-landmark" aria-label="Appearance"> <div id="vector-appearance-pinned-container" class="vector-pinned-container"> <div id="vector-appearance" class="vector-appearance vector-pinnable-element"> <div class="vector-pinnable-header vector-appearance-pinnable-header vector-pinnable-header-pinned" data-feature-name="appearance-pinned" data-pinnable-element-id="vector-appearance" data-pinned-container-id="vector-appearance-pinned-container" data-unpinned-container-id="vector-appearance-unpinned-container" > <div class="vector-pinnable-header-label">Appearance</div> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-pin-button" data-event-name="pinnable-header.vector-appearance.pin">move to sidebar</button> <button class="vector-pinnable-header-toggle-button vector-pinnable-header-unpin-button" data-event-name="pinnable-header.vector-appearance.unpin">hide</button> </div> </div> </div> </nav> </div> </div> <div id="bodyContent" class="vector-body" aria-labelledby="firstHeading" data-mw-ve-target-container> <div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"><span class="mw-redirectedfrom">(Redirected from <a href="/w/index.php?title=Niacin_receptor_1&redirect=no" class="mw-redirect" title="Niacin receptor 1">Niacin receptor 1</a>)</span></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Protein-coding gene in the species Homo sapiens</div> <table class="infobox" style="width:26.4em"><tbody><tr><th colspan="4" style="text-align:center;font-size:125%;font-weight:bold">HCAR2</th></tr><tr><td colspan="4" style="text-align:center"></td></tr><tr><th colspan="4" style="text-align:center;background-color:#ddd">Identifiers</th></tr><tr><th scope="row" style="background-color:#c3fdb8"><span class="plainlinks"><a href="/wiki/Gene_nomenclature" title="Gene nomenclature">Aliases</a></span></th><td colspan="3" style="background:#eee"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/24827">HCAR2</a></span>, GPR109A, HCA2, HM74a, HM74b, NIACR1, PUMAG, Puma-g, Niacin receptor 1, hydroxycarboxylic acid receptor 2</td></tr><tr><th scope="row" style="background-color:#c3fdb8">External IDs</th><td colspan="3" style="background-color:#eee"><span class="plainlinks"><a href="/wiki/Mendelian_Inheritance_in_Man" class="mw-redirect" title="Mendelian Inheritance in Man">OMIM</a>: <a rel="nofollow" class="external text" href="https://omim.org/entry/609163">609163</a>; <a href="/wiki/Mouse_Genome_Informatics" title="Mouse Genome Informatics">MGI</a>: <a rel="nofollow" class="external text" href="http://www.informatics.jax.org/marker/MGI:1933383">1933383</a>; <a href="/wiki/HomoloGene" title="HomoloGene">HomoloGene</a>: <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=HomoloGene&list_uids=4391">4391</a>; <a href="/wiki/GeneCards" title="GeneCards">GeneCards</a>: <a rel="nofollow" class="external text" href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=HCAR2">HCAR2</a>; <a href="/wiki/Orthologous_MAtrix" title="Orthologous MAtrix">OMA</a>:<a rel="nofollow" class="external text" href="https://omabrowser.org/oma/vps/ENSG00000182782">HCAR2 - orthologs</a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd">Gene location (<a href="/wiki/Human_genome" title="Human genome">Human</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span typeof="mw:File"><a href="/wiki/File:Ideogram_human_chromosome_12.svg" class="mw-file-description" title="Chromosome 12 (human)"><img alt="Chromosome 12 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Ideogram_human_chromosome_12.svg/300px-Ideogram_human_chromosome_12.svg.png" decoding="async" width="300" height="120" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Ideogram_human_chromosome_12.svg/450px-Ideogram_human_chromosome_12.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e7/Ideogram_human_chromosome_12.svg/600px-Ideogram_human_chromosome_12.svg.png 2x" data-file-width="474" data-file-height="189" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:#eee"><span class="plainlinks"><a href="/wiki/Chromosome_12_(human)" class="mw-redirect" title="Chromosome 12 (human)">Chromosome 12 (human)</a><sup id="cite_ref-refGRCh38Ensembl_1-0" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Human_chromosome_12_ideogram.svg" class="mw-file-description" title="Chromosome 12 (human)"><img alt="Chromosome 12 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/3/38/Human_chromosome_12_ideogram.svg/300px-Human_chromosome_12_ideogram.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/38/Human_chromosome_12_ideogram.svg/450px-Human_chromosome_12_ideogram.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/38/Human_chromosome_12_ideogram.svg/600px-Human_chromosome_12_ideogram.svg.png 2x" data-file-width="1125" data-file-height="216" /></a></span><div style="position: absolute; left: 265.39905325667px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for HCAR2"><img alt="Genomic location for HCAR2" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 271.4px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for HCAR2"><img alt="Genomic location for HCAR2" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:#eee"><span class="plainlinks">12q24.31</span></td><th scope="row" style="background-color:#c3fdb8">Start</th><td style="background-color:#eee"><span class="plainlinks">122,701,293 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-1" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:#c3fdb8">End</th><td style="background-color:#eee"><span class="plainlinks">122,703,357 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-2" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd">Gene location (<a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span typeof="mw:File"><a href="/wiki/File:Ideogram_house_mouse_chromosome_5.svg" class="mw-file-description" title="Chromosome 5 (mouse)"><img alt="Chromosome 5 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/c/c0/Ideogram_house_mouse_chromosome_5.svg/260px-Ideogram_house_mouse_chromosome_5.svg.png" decoding="async" width="260" height="111" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/c0/Ideogram_house_mouse_chromosome_5.svg/390px-Ideogram_house_mouse_chromosome_5.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/c0/Ideogram_house_mouse_chromosome_5.svg/520px-Ideogram_house_mouse_chromosome_5.svg.png 2x" data-file-width="470" data-file-height="200" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:#eee"><span class="plainlinks">Chromosome 5 (mouse)<sup id="cite_ref-refGRCm38Ensembl_2-0" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Ideogram_of_house_mouse_chromosome_5.svg" class="mw-file-description" title="Chromosome 5 (mouse)"><img alt="Chromosome 5 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f9/Ideogram_of_house_mouse_chromosome_5.svg/300px-Ideogram_of_house_mouse_chromosome_5.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f9/Ideogram_of_house_mouse_chromosome_5.svg/450px-Ideogram_of_house_mouse_chromosome_5.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f9/Ideogram_of_house_mouse_chromosome_5.svg/600px-Ideogram_of_house_mouse_chromosome_5.svg.png 2x" data-file-width="1200" data-file-height="231" /></a></span><div style="position: absolute; left: 234.81705614369px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for HCAR2"><img alt="Genomic location for HCAR2" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 240.8px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for HCAR2"><img alt="Genomic location for HCAR2" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:#eee"><span class="plainlinks">5|5 F</span></td><th scope="row" style="background-color:#c3fdb8">Start</th><td style="background-color:#eee"><span class="plainlinks">124,001,633 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-1" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:#c3fdb8">End</th><td style="background-color:#eee"><span class="plainlinks">124,003,562 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-2" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Gene_expression" title="Gene expression">RNA expression</a> pattern</th></tr><tr><th scope="row" style="background-color:#c3fdb8"><a rel="nofollow" class="external text" href="https://www.bgee.org/">Bgee</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th><b><a href="/wiki/Human_genome" title="Human genome">Human</a></b></th><th><b><a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a> (ortholog)</b></th></tr><tr><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000182782">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">blood</li><br /><li style="line-height: 137%;">olfactory zone of nasal mucosa</li><br /><li style="line-height: 137%;">granulocyte</li><br /><li style="line-height: 137%;">skin of abdomen</li><br /><li style="line-height: 137%;">gonad</li><br /><li style="line-height: 137%;">skin of leg</li><br /><li style="line-height: 137%;">spleen</li><br /><li style="line-height: 137%;">bone marrow</li><br /><li style="line-height: 137%;">minor salivary glands</li><br /><li style="line-height: 137%;">subcutaneous adipose tissue</li></ul></div></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSMUSG00000045502">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">granulocyte</li><br /><li style="line-height: 137%;">esophagus</li><br /><li style="line-height: 137%;">lip</li><br /><li style="line-height: 137%;">skin of external ear</li><br /><li style="line-height: 137%;">morula</li><br /><li style="line-height: 137%;">subcutaneous adipose tissue</li><br /><li style="line-height: 137%;">skin of back</li><br /><li style="line-height: 137%;">transitional epithelium of urinary bladder</li><br /><li style="line-height: 137%;">trachea</li><br /><li style="line-height: 137%;">skin of abdomen</li></ul></div></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000182782">More reference expression data</a></span></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a rel="nofollow" class="external text" href="http://biogps.org/">BioGPS</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><td colspan="4" style="text-align:center;background-color:#eee">n/a</td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span class="plainlinks"></span></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Gene_ontology" class="mw-redirect" title="Gene ontology">Gene ontology</a></th></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Molecular function</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070553">nicotinic acid receptor activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0004930">G protein-coupled receptor activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/">signal transducer activity</a></li></ul> </div></td></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Cellular component</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016021">integral component of membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0030054">cell junction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005886">plasma membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016020">membrane</a></li></ul> </div></td></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Biological process</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006915">apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0050995">negative regulation of lipid catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070165">positive regulation of adiponectin secretion</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007165">signal transduction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0033031">positive regulation of neutrophil apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0001781">neutrophil apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007186">G protein-coupled receptor signaling pathway</a></li></ul> </div></td></tr><tr><td colspan="4" style="background-color:#eee;text-align:center">Sources:<a rel="nofollow" class="external text" href="http://amigo.geneontology.org/">Amigo</a> / <a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/QuickGO/">QuickGO</a></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Orthologs" class="mw-redirect" title="Orthologs">Orthologs</a></th></tr><tr><th scope="row" style="background-color:#c3fdb8">Species</th><td><b>Human</b></td><td><b>Mouse</b></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/Entrez" title="Entrez">Entrez</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=338442&rn=1">338442</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=80885&rn=1">80885</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/Ensembl" class="mw-redirect" title="Ensembl">Ensembl</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000182782;db=core">ENSG00000182782</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Mus_musculus/geneview?gene=ENSMUSG00000045502;db=core">ENSMUSG00000045502</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/UniProt" title="UniProt">UniProt</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/Q8TDS4">Q8TDS4</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/Q9EP66">Q9EP66</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">RefSeq (mRNA)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_177551">NM_177551</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_030701">NM_030701</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">RefSeq (protein)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_808219">NP_808219</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_109626">NP_109626</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">Location (UCSC)</th><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&position=chr12:122701293-122703357">Chr 12: 122.7 – 122.7 Mb</a></span></td><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Mouse&db=mm0&position=chr5:124001633-124003562">Chr 5: 124 – 124 Mb</a></span></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/PubMed" title="PubMed">PubMed</a> search</th><td><span class="plainlinks"><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></span></td><td><span class="plainlinks"><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><a href="/wiki/Wikidata" title="Wikidata">Wikidata</a></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="2" style="background-color:#eee;text-align:center"><a href="https://www.wikidata.org/wiki/Q18055221" class="extiw" title="d:Q18055221">View/Edit Human</a></td><td colspan="2" style="background-color:#eee;text-align:center"><a href="https://www.wikidata.org/wiki/Q18269736" class="extiw" title="d:Q18269736">View/Edit Mouse</a></td></tr></tbody></table></td></tr></tbody></table> <p><b>Hydroxycarboxylic acid receptor 2</b> (HCA<sub>2</sub>), also known as GPR109A and niacin receptor 1 (NIACR1), is a <a href="/wiki/Protein" title="Protein">protein</a> which in humans is encoded (its formation is directed) by the <i>HCAR2</i> <a href="/wiki/Gene" title="Gene">gene</a> and in rodents by the <i>Hcar2</i> gene.<sup id="cite_ref-pmid21454438_5-0" class="reference"><a href="#cite_note-pmid21454438-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12044878_6-0" class="reference"><a href="#cite_note-pmid12044878-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12522134_7-0" class="reference"><a href="#cite_note-pmid12522134-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12646212_8-0" class="reference"><a href="#cite_note-pmid12646212-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> The human <i>HCAR2</i> gene is located on the long (i.e., "q") arm of <a href="/wiki/Chromosome_12" title="Chromosome 12">chromosome 12</a> at position 24.31 (notated as 12q24.31).<sup id="cite_ref-entrez_9-0" class="reference"><a href="#cite_note-entrez-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Like the two other <a href="/wiki/Hydroxycarboxylic_acid_receptor" title="Hydroxycarboxylic acid receptor">hydroxycarboxylic acid receptors</a>, <a href="/wiki/HCA1" class="mw-redirect" title="HCA1">HCA<sub>1</sub></a> and <a href="/wiki/HCA3" class="mw-redirect" title="HCA3">HCA<sub>3</sub></a>, HCA<sub>2</sub> is a <a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">G protein-coupled receptor</a> (GPCR) located on the <a href="/wiki/Cell_membrane" title="Cell membrane">surface membrane</a> of cells.<sup id="cite_ref-pmid21454438_5-1" class="reference"><a href="#cite_note-pmid21454438-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-IUPHAR-DB_HCAR_family_page_10-0" class="reference"><a href="#cite_note-IUPHAR-DB_HCAR_family_page-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> HCA<sub>2</sub> binds and thereby is activated by <a href="/wiki/%CE%92-Hydroxybutyric_acid" title="Β-Hydroxybutyric acid">D-β-hydroxybutyric acid</a> (hereafter termed β-hydroxybutyric acid), <a href="/wiki/Butyric_acid" title="Butyric acid">butyric acid</a>, and <a href="/wiki/Niacin_(substance)" class="mw-redirect" title="Niacin (substance)">niacin</a> (also known as nicotinic acid).<sup id="cite_ref-pmid12522134_7-1" class="reference"><a href="#cite_note-pmid12522134-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12646212_8-1" class="reference"><a href="#cite_note-pmid12646212-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> β-Hydroxybutyric and butyric acids are regarded as the <a href="/wiki/Endogeny_(biology)" title="Endogeny (biology)">endogenous</a> agents that activate HCA<sub>2</sub>. Under normal conditions, niacin's blood levels are too low to do so: it is given as a drug in high doses in order to reach levels that activate HCA<sub>2</sub>.<sup id="cite_ref-pmid36057320_11-0" class="reference"><a href="#cite_note-pmid36057320-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p><p>β-Hydroxybutyric acid, butyric acid, and niacin have actions that are independent of HCA<sub>2</sub>. For example: <b>1)</b> β-hydroxybutyric acid activates <a href="/wiki/Free_fatty_acid_receptor_3" title="Free fatty acid receptor 3">free fatty acid receptor 3</a><sup id="cite_ref-pmid31685604_12-0" class="reference"><a href="#cite_note-pmid31685604-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> and inhibits some <a href="/wiki/Histone_deacetylases" class="mw-redirect" title="Histone deacetylases">histone deacetylases</a> that regulate the <a href="/wiki/Gene_expression#Regulation_of_gene_expression" title="Gene expression">expression</a> of various genes, increase <a href="/wiki/Mitochondrial" class="mw-redirect" title="Mitochondrial">mitochondrial</a> <a href="/wiki/Adenosine_triphosphate" title="Adenosine triphosphate">adenosine triphosphate</a> production, and promote <a href="/wiki/Antioxidant" title="Antioxidant">antioxidant</a> defenses;<sup id="cite_ref-pmid36204834_13-0" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> <b>2)</b> butyric acid activates <a href="/wiki/Free_fatty_acid_receptor_2" title="Free fatty acid receptor 2">free fatty acid receptor 2</a> and like β-hydroxybutyric acid activates free fatty acid receptor 3<sup id="cite_ref-pmid33495026_14-0" class="reference"><a href="#cite_note-pmid33495026-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> and inhibits some histone deacetylases;<sup id="cite_ref-pmid26868600_15-0" class="reference"><a href="#cite_note-pmid26868600-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> and <b>3)</b> niacin is an NAD<sup>+</sup> precursor (see <a href="/wiki/Nicotinamide_adenine_dinucleotide" title="Nicotinamide adenine dinucleotide">nicotinamide adenine dinucleotide</a>) which when converted to NAD<sup>+</sup> can alter over 500 enzymatic reactions that play key roles in regulating <a href="/wiki/Inflammation" title="Inflammation">inflammation</a>, <a href="/wiki/Mitochondrion" title="Mitochondrion">mitochondrion</a> functions, <a href="/wiki/Autophagy" title="Autophagy">autophagy</a>, and <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>.<sup id="cite_ref-pmid36204834_13-1" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> Consequently, studies examining the functions of HCA<sub>2</sub> based on the actions of butyric acid, β-hydroxybutyric acid, niacin, or other HCA<sub>2</sub> activators need to provide data indicating that they actually do so by activating HCA<sub>2</sub>. One commonly used way to do this is to show that the activators have no or reduced effects on <i>Hca2</i> <a href="/wiki/Gene_knockout" title="Gene knockout">gene knockout</a> cells or animals (i.e., cells or animals that had their <i>HCa2</i> genes removed or inactivated) or <a href="/wiki/Gene_knockdown" title="Gene knockdown">gene knockdown</a> cells or animals (i.e., cells or animals that had their <i>HCa2</i> genes ability to express HCA<sub>2</sub> greatly reduced).<sup id="cite_ref-pmid36339405_16-0" class="reference"><a href="#cite_note-pmid36339405-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> The studies reported here on HCA<sub>2</sub> activators focus on those that included experiments in <i>Hca2</i> gene knockout and/or knockdown cells and animals. </p><p>Studies, done mostly in animals and the cells taken from animals or humans, show or suggest that HCA<sub>2</sub> functions to <b>1)</b> inhibit <a href="/wiki/Lipolysis" title="Lipolysis">lipolysis</a> and <b>2)</b> inhibit inflammation and thereby suppress the development of certain diseases in which inflammation contributes to their development and/or severity.<sup id="cite_ref-pmid36204834_13-2" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid26773933_17-0" class="reference"><a href="#cite_note-pmid26773933-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid28446062_18-0" class="reference"><a href="#cite_note-pmid28446062-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> These diseases include: <a href="/wiki/Atherosclerosis" title="Atherosclerosis">atherosclerosis</a>,<sup id="cite_ref-pmid32093510_19-0" class="reference"><a href="#cite_note-pmid32093510-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Stroke" title="Stroke">stroke</a>, <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a>, <a href="/wiki/Parkinson%27s_disease" title="Parkinson's disease">Parkinson's disease</a>, <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>, pathological pain (i.e. pain due to the abnormal activation of <a href="/wiki/Neurons" class="mw-redirect" title="Neurons">neurons</a>),<sup id="cite_ref-pmid36204834_13-3" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Mastitis" title="Mastitis">mastitis</a>,<sup id="cite_ref-pmid34803497_20-0" class="reference"><a href="#cite_note-pmid34803497-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Hepatitis" title="Hepatitis">hepatitis</a> due to heavy alcohol consumption,<sup id="cite_ref-pmid29705237_21-0" class="reference"><a href="#cite_note-pmid29705237-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Inflammatory_bowel_diseases" class="mw-redirect" title="Inflammatory bowel diseases">inflammatory bowel diseases</a>, cancer of the <a href="/wiki/Colon_(anatomy)" class="mw-redirect" title="Colon (anatomy)">colon</a>,<sup id="cite_ref-pmid24412617_22-0" class="reference"><a href="#cite_note-pmid24412617-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> and, possibly, <a href="/wiki/Psoriasis" title="Psoriasis">psoriasis</a><sup id="cite_ref-pmid37004600_23-0" class="reference"><a href="#cite_note-pmid37004600-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> and brain damage due to heavy alcohol consumption.<sup id="cite_ref-pmid36709599_24-0" class="reference"><a href="#cite_note-pmid36709599-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="HCA2_and_HCA3_homodimer_and_heterodimer_proteins">HCA<sub>2</sub> and HCA<sub>3</sub> homodimer and heterodimer proteins</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=1" title="Edit section: HCA2 and HCA3 homodimer and heterodimer proteins"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>HCA<sub>2</sub> is commonly formed and regarded as a <a href="/wiki/Protein_dimer" title="Protein dimer">homodimer</a>, i.e. to be composed of two adjoined HCA<sub>2</sub> proteins. However, a <a href="/wiki/Protein_dimer" title="Protein dimer">heterodimer</a> composed of the HCA<sub>2</sub> protein adjoined to the HCA<sub>3</sub> protein has been detected in human embryonic kidney <a href="/wiki/HEK_293_cells" title="HEK 293 cells">HEK 293 cells</a>. The human <i>HCAR2</i> and <i>HCAR3</i> genes sit next to each other on chromosome 12 at position 24.31 and have an amino acid <a href="/wiki/Sequence_homology" title="Sequence homology">sequence homology</a> greater than 95%. While there appears to be no significant difference in the responses triggered by activation of cells expressing the HCA<sub>2</sub> homodimer <i>versus</i> the HCA<sub>2</sub>/HCA<sub>3</sub> heterodimer proteins, more studies are needed to confirm this.<sup id="cite_ref-pmid36204834_13-4" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> Furthermore: <b>1)</b> HCA<sub>2</sub> and HCA<sub>1</sub> are found in most mammalian species but HCA<sub>3</sub> is found only in higher primates<sup id="cite_ref-pmid21454438_5-2" class="reference"><a href="#cite_note-pmid21454438-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> and <b>2)</b> monodimeric HCA<sub>2</sub> and HCA<sub>3</sub> proteins may show very different ligand sensitivities, e.g., niacin binds to and activates HCA<sub>2</sub> but does not or only weakly binds to and activates HCA<sub>3</sub>.<sup id="cite_ref-pmid35900600_25-0" class="reference"><a href="#cite_note-pmid35900600-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Studies on HCA<sub>2</sub> in human cells and tissues have not determined the extent to which these cells and tissues also express HCA<sub>3</sub> and form HCA<sub>3</sub>-HCA<sub>3</sub> heterodimers. The studies cited here may need to be revised if future studies find that HCA<sub>2</sub>-HCA<sub>3</sub> heterodimers are involved in the effects of "HCA<sub>2</sub> activators".<sup id="cite_ref-pmid36204834_13-5" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Cells_and_tissues_expressing_HCA2">Cells and tissues expressing HCA<sub>2</sub></h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=2" title="Edit section: Cells and tissues expressing HCA2"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>HCA<sub>2</sub> is expressed by: <b>1)</b> certain cells in the <a href="/wiki/Immune_system" title="Immune system">immune system</a>, e.g., <a href="/wiki/Neutrophils" class="mw-redirect" title="Neutrophils">neutrophils</a>, <a href="/wiki/Monocytes" class="mw-redirect" title="Monocytes">monocytes</a>, <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>, <a href="/wiki/Dermal" class="mw-redirect" title="Dermal">dermal</a> <a href="/wiki/Dendritic_cells" class="mw-redirect" title="Dendritic cells">dendritic cells</a>,<sup id="cite_ref-pmid28446062_18-1" class="reference"><a href="#cite_note-pmid28446062-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Lymphocytes" class="mw-redirect" title="Lymphocytes">lymphocytes</a>;<sup id="cite_ref-pmid36204834_13-6" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> <b>2)</b> cells in the <a href="/wiki/Small_intestine" title="Small intestine">small intestine</a> and <a href="/wiki/Colon_(anatomy)" class="mw-redirect" title="Colon (anatomy)">colon</a> <a href="/wiki/Intestinal_epithelium" title="Intestinal epithelium">epithelum</a> that face the intestinal <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">lumen</a>;<sup id="cite_ref-pmid33897470_26-0" class="reference"><a href="#cite_note-pmid33897470-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> <b>3)</b> the skin's <a href="/wiki/Epithelium" title="Epithelium">epithelial cells</a>, <a href="/wiki/Keratinocytes" class="mw-redirect" title="Keratinocytes">keratinocytes</a>, and <a href="/wiki/Langerhans_cells" class="mw-redirect" title="Langerhans cells">Langerhans cells</a>;<sup id="cite_ref-pmid28087125_27-0" class="reference"><a href="#cite_note-pmid28087125-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> <b>4)</b> <a href="/wiki/White_adipose_tissue" title="White adipose tissue">brown</a> and <a href="/wiki/White_adipose_tissue" title="White adipose tissue">white adipose tissue</a> fat cells;<sup id="cite_ref-pmid35912645_28-0" class="reference"><a href="#cite_note-pmid35912645-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> <b>5)</b> cells in the <a href="/wiki/Mammary_gland" title="Mammary gland">mammary gland</a>'s <a href="/wiki/Epithelium" title="Epithelium">epithelium</a>;<sup id="cite_ref-pmid34803497_20-1" class="reference"><a href="#cite_note-pmid34803497-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> <b>6)</b> <a href="/wiki/Hepatocytes" class="mw-redirect" title="Hepatocytes">hepatocytes</a>; <b>7)</b> <a href="/wiki/Multinucleate" title="Multinucleate">multinucleated</a> <a href="/wiki/Osteoclasts" class="mw-redirect" title="Osteoclasts">osteoclasts</a> in bone tissues; <b>8)</b> kidney <a href="/wiki/Podocytes" class="mw-redirect" title="Podocytes">podocytes</a>;<sup id="cite_ref-pmid36204834_13-7" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> and <b>9)</b> cells in the <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a>, e.g., <a href="/wiki/Microglia" title="Microglia">microglia</a> cells in the brain's <a href="/wiki/Cerebral_cortex" title="Cerebral cortex">cerebral cortex</a> and <a href="/wiki/Hippocampus" title="Hippocampus">hippocampus</a>,<sup id="cite_ref-pmid36709599_24-1" class="reference"><a href="#cite_note-pmid36709599-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> cells in the eye's <a href="/wiki/Retinal_pigment_epithelium" title="Retinal pigment epithelium">retinal pigment epithelium</a>,<sup id="cite_ref-pmid35649469_29-0" class="reference"><a href="#cite_note-pmid35649469-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid22427566_30-0" class="reference"><a href="#cite_note-pmid22427566-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> the <a href="/wiki/Astrocytes" class="mw-redirect" title="Astrocytes">astrocytes</a> and <a href="/wiki/Neurons" class="mw-redirect" title="Neurons">neurons</a> in the brain's <a href="/wiki/Rostral_ventrolateral_medulla" title="Rostral ventrolateral medulla">rostral ventrolateral medulla</a>, and the <a href="/wiki/Peripheral_nervous_system" title="Peripheral nervous system">peripheral nervous system</a>'s <a href="/wiki/Schwann_cell" title="Schwann cell">Schwann</a> and <a href="/wiki/Satellite_glial_cell" title="Satellite glial cell">satellite glial cells</a>.<sup id="cite_ref-pmid36204834_13-8" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="HCA2_activating_agents">HCA<sub>2</sub> activating agents</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=3" title="Edit section: HCA2 activating agents"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In addition to butyric acid, β-hydroxybutyric acid, and niacin, the following agents have been reported to activate HCA<sub>2</sub>: <a href="/wiki/Monomethyl_fumarate" title="Monomethyl fumarate">monomethyl fumarate</a>,<sup id="cite_ref-pmid28087125_27-1" class="reference"><a href="#cite_note-pmid28087125-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">dimethyl fumarate</a> (dimethyl fumarate is a <a href="/wiki/Prodrug" title="Prodrug">prodrug</a>, i.e. it does not directly activate HCA<sub>2</sub> but is rapidly converted in animal intestines to monomethyl fumarate<sup id="cite_ref-pmid37004600_23-1" class="reference"><a href="#cite_note-pmid37004600-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid35569547_31-0" class="reference"><a href="#cite_note-pmid35569547-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup>),<sup id="cite_ref-pmid36204834_13-9" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid29763776_32-0" class="reference"><a href="#cite_note-pmid29763776-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Acifran" title="Acifran">Acifran</a> (Acifran also binds to HCA<sub>3</sub> but with less affinity for it than for HCA<sub>3</sub><sup id="cite_ref-pmid35900600_25-1" class="reference"><a href="#cite_note-pmid35900600-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup>), <a href="/wiki/Acipimox" title="Acipimox">Acipimox</a>, <a href="/wiki/SCH_900271" title="SCH 900271">SCH 900271</a>,<sup id="cite_ref-pmid28087125_27-2" class="reference"><a href="#cite_note-pmid28087125-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> MK-6892,<sup id="cite_ref-pmid20184326_33-0" class="reference"><a href="#cite_note-pmid20184326-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> MK-1903,<sup id="cite_ref-pmid22435740_34-0" class="reference"><a href="#cite_note-pmid22435740-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> GSK256073,<sup id="cite_ref-pmid23701262_35-0" class="reference"><a href="#cite_note-pmid23701262-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> and N2L.<sup id="cite_ref-pmid31846627_36-0" class="reference"><a href="#cite_note-pmid31846627-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="HCA2's_function_in_lipolysis"><span id="HCA2.27s_function_in_lipolysis"></span>HCA<sub>2</sub>'s function in lipolysis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=4" title="Edit section: HCA2's function in lipolysis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Lipolysis is the <a href="/wiki/Metabolic_pathway" title="Metabolic pathway">metabolic pathway</a> in which <a href="/wiki/Triglycerides" class="mw-redirect" title="Triglycerides">triglycerides</a> are <a href="/wiki/Hydrolyzed" class="mw-redirect" title="Hydrolyzed">hydrolyzed</a>, i.e., enzymatically broken down, into their component free <a href="/wiki/Fatty_acids" class="mw-redirect" title="Fatty acids">fatty acids</a> and <a href="/wiki/Glycerol" title="Glycerol">glycerol</a>. The activation of this pathway leads fat cells to release the newly freed fatty acids into the circulation and thereby raises <a href="/wiki/Serum_(blood)" title="Serum (blood)">serum</a> free fatty acid levels; the inhibition of this lipolysis leads to falls in serum free fatty acid levels. The intravascular injection of niacin into control mice rapidly reduced their serum fatty acid levels but did not do so in <i>Hcar2</i> <a href="/wiki/Gene_knockout" title="Gene knockout">gene knockout</a> mice. Thus, HCA<sub>2</sub> functions to inhibit lipolysis and lower serum fatty acid levels in mice.<sup id="cite_ref-pmid19141678_37-0" class="reference"><a href="#cite_note-pmid19141678-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> Niacin likewise inhibits lipolysis to lower free fatty acid <a href="/wiki/Blood_plasma" title="Blood plasma">plasma</a> levels in humans. Furthermore, the HCA<sub>2</sub>-activating drug, MK-1903, when taken orally by healthy volunteers in <a href="/wiki/Clinical_trial#Phases" title="Clinical trial">phase 1 and 2</a> <a href="/wiki/Clinical_trial" title="Clinical trial">clinical trials</a>, dramatically lowered their plasma free fatty acids levels. Like niacin, <a href="/wiki/Flushing_(physiology)" title="Flushing (physiology)">flushing</a> was the drug's only major adverse effect. Unlike niacin, however, MK-1903 had far less effects than niacin on the plasma levels of <a href="/wiki/Triglycerides" class="mw-redirect" title="Triglycerides">triglycerides</a> and HDL-c] (i.e., <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a>-associated <a href="/wiki/High_density_lipoprotein" class="mw-redirect" title="High density lipoprotein">High density lipoprotein</a>) which are niacin's therapeutic targets for treating primary <a href="/wiki/Hyperlipidemia" title="Hyperlipidemia">hyperlipidemia</a> and <a href="/wiki/Hypertriglyceridemia" title="Hypertriglyceridemia">hypertriglyceridemia</a>. These findings suggest but need further studies to determine if niacin and Mk-1903 inhibit lipolysis in humans by activating HCA<sub>2</sub>.<sup id="cite_ref-pmid22914621_38-0" class="reference"><a href="#cite_note-pmid22914621-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> Studies suggest that HCA<sub>1</sub> and, possibly, HCA<sub>3</sub> also inhibit lipolysis.<sup id="cite_ref-pmid28087125_27-3" class="reference"><a href="#cite_note-pmid28087125-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="HCA2's_functions_in_various_diseases"><span id="HCA2.27s_functions_in_various_diseases"></span>HCA<sub>2</sub>'s functions in various diseases</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=5" title="Edit section: HCA2's functions in various diseases"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Atherosclerosis">Atherosclerosis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=6" title="Edit section: Atherosclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Atherosclerosis is a chronic inflammatory <a href="/wiki/Arterial" class="mw-redirect" title="Arterial">arterial</a> disease that can cause the narrowing or occlusion of <a href="/wiki/Arteries" class="mw-redirect" title="Arteries">arteries</a> and thereby various <a href="/wiki/Cardiovascular_diseases" class="mw-redirect" title="Cardiovascular diseases">cardiovascular diseases</a> such as <a href="/wiki/Heart_attacks" class="mw-redirect" title="Heart attacks">heart attacks</a> and <a href="/wiki/Stroke" title="Stroke">strokes</a>. In a murine <a href="/wiki/Apolipoprotein_E#Inflammation" title="Apolipoprotein E">ApoE−/− model of atherosclerosis</a>, mice were feed a <a href="/wiki/Cholesterol" title="Cholesterol">cholesterol</a>‐rich (i.e., atherosclerosis-promoting) diet concurrently with β-hydroxybutyric acid, nicotine, or salt water daily for 9 weeks. The <a href="/wiki/Aortas" class="mw-redirect" title="Aortas">aortas</a> of β-hydroxybutyric acid-treated and niacin-treated mice had far less <a href="/wiki/Histology" title="Histology">histological</a> evidence of atherosclerosis (i.e., less <a href="/wiki/Atherosclerotic_plaques" class="mw-redirect" title="Atherosclerotic plaques">atherosclerotic plaques</a>, lipid depositions, and infiltrating <a href="/wiki/Macrophage_polarization#M1" title="Macrophage polarization">M1</a> inflammation-promoting <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>) than salt water-treated mice. β-Hydroxybutyric acid-fed mice also had significantly lower blood <a href="/wiki/Blood_plasma" title="Blood plasma">plasma</a> levels of three pro-inflammatory cytokines, <a href="/wiki/Tumor_necrosis_factor-%CE%B1" class="mw-redirect" title="Tumor necrosis factor-α">tumor necrosis factor-α</a>, <a href="/wiki/Interleukin-6" class="mw-redirect" title="Interleukin-6">interleukin-6</a>, and <a href="/wiki/Interleukin-1%CE%B2" class="mw-redirect" title="Interleukin-1β">interleukin-1β</a>, than salt water-treated mice. Further studies found that <b>1)</b> β-hydroxybutyric acid inhibited <a href="/wiki/Lipopolysaccharide" title="Lipopolysaccharide">lipopolysaccharide</a>-simulated maturation of normal <a href="/wiki/Bone_marrow" title="Bone marrow">bone marrow</a>‐derived macrophages to M1 macrophages but did not do so in macrophages taken from the bone marrows of <i>Hcar2</i> gene knockout mice and <b>2)</b> mice constructed to have <i>Hcar2</i> gene knockout but no normal bone marrow cells who were treated with β-hydroxybutyric acid had significantly more evidence of arterial inflammation and atherosclerosis than β-hydroxybutyric acid-treated mice who had normal bone marrow cells. These results indicate that the anti-inflammatory and anti-atherosclerotic effects of β-hydroxybutyric acid in ApoE−/− mice depend on bone‐marrow‐derived HCA<sub>2</sub>-expressing cells, possibly M1 macrophages. Further studies are needed to determine if HCA<sub>2</sub> acts to suppress the development and/or progression of human atherosclerosis.<sup id="cite_ref-pmid36204834_13-10" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid33977048_39-0" class="reference"><a href="#cite_note-pmid33977048-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Stroke">Stroke</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=7" title="Edit section: Stroke"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Stroke is the development of persistent brain disfunction caused by the interruption of blow flow and subsequent damage to the brain. The inflammation that develops in damaged areas of the brain causes further brain damage.<sup id="cite_ref-pmid36204834_13-11" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> Studies have reported that HCA<sub>2</sub> reduces the inflammation and thereby the extent of brain damage in animal models of stroke. Mice that had a distal portion of their <a href="/wiki/Middle_cerebral_arteries" class="mw-redirect" title="Middle cerebral arteries">middle cerebral arteries</a> occluded were treated with either β-hydroxybutyric acid or niacin shortly before and up to 48 hours after occluding the artery. β-Hydroxybutyric acid-treated mice had less damaged brain tissue and better performances in corner testing (i.e., control mice but not β-hydroxybutyric acid-treated mice tended to turn toward the side opposite the damaged brain site). β-Hydroxybutyric acid did not reduce the brain damage or improve corner test performance in <i>Hca2</i> gene knockout mice. Niacin likewise reduced the size of the damaged brain site in normal but not in <i>Hca2</i> gene knockout mice. And, mice feed a <a href="/wiki/Ketogenic_diet" title="Ketogenic diet">ketogenic diet</a> for 14 days (which increased their plasma levels of β-hydroxybutyric acid) also had reductions in the size of their brains' damaged sites. The diet had no such effect in<i>Hca2</i> gene knockout mice. Further studies indicated that the effect of niacin in reducing the size of damage brain sites involved the stimulation of HCA<sub>2</sub>-bearing <a href="/wiki/Monocytes" class="mw-redirect" title="Monocytes">monocytes</a> and/or <a href="/wiki/Macrophage" title="Macrophage">macrophages</a> to produce <a href="/wiki/Prostaglandin_D2" title="Prostaglandin D2">prostaglandin D2</a>.<sup id="cite_ref-pmid24845831_40-0" class="reference"><a href="#cite_note-pmid24845831-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> (Prostaglandin D2 has anti-inflammatory actions.<sup id="cite_ref-pmid35367459_41-0" class="reference"><a href="#cite_note-pmid35367459-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup>) Finally, several other studies, while not examining <i>Hcar2</i> gene knockout or knockdown animals, reported that β-hydroxybutyric acid, niacin. monomethyl fumarate, and dimethyl fumarate reduced the inflammation, tissue damage, and/or symptoms in middle cerebral artery occlusion animal models of stroke. These results indicate that HCA<sub>2</sub> reduces the clinical consequences of stroke in rodents and support further studies that may lead to the development of novel treatments for stroke in humans.<sup id="cite_ref-pmid36204834_13-12" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Alzheimer's_disease"><span id="Alzheimer.27s_disease"></span>Alzheimer's disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=8" title="Edit section: Alzheimer's disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Alzheimer's disease is a form of <a href="/wiki/Dementia" title="Dementia">dementia</a> that is associated with the activation of the brain's pro-inflammatory microglial cells; the increased production of pro-inflammatory <a href="/wiki/Cytokines" class="mw-redirect" title="Cytokines">cytokines</a>; and the accumulation in the brain of <b>a)</b> extracellular <a href="/wiki/Amyloid_plaques" title="Amyloid plaques">amyloid plaques</a> consisting of <a href="/wiki/Protein_folding#Protein_misfolding" title="Protein folding">misfolded</a> <a href="/wiki/Amyloid-%CE%B2" class="mw-redirect" title="Amyloid-β">amyloid-β</a> protein, <b>b)</b> <a href="/wiki/Amyloid-beta_precursor_protein" title="Amyloid-beta precursor protein">amyloid-beta precursor protein</a> (which is <a href="/wiki/Enzyme" title="Enzyme">enzymatically</a> broken down to amyloid-β protein), and <b>c)</b> intracellular aggregates of <a href="/wiki/Hyperphosphorylated" class="mw-redirect" title="Hyperphosphorylated">hyperphosphorylated</a> <a href="/wiki/Tau_protein" title="Tau protein">tau protein</a>. Individuals with Alzheimer's disease commonly show progressively worsening declines in <a href="/wiki/Cognition" title="Cognition">cognitive</a>, behavioral, and sensorimotor functions<sup id="cite_ref-pmid31914599_42-0" class="reference"><a href="#cite_note-pmid31914599-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> along with increasing accumulations of aggregated amyloid-β proteins (which may be a key factor in the development of Alzheimer's disease).<sup id="cite_ref-pmid35320002_43-0" class="reference"><a href="#cite_note-pmid35320002-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> In the 5XFAD murine model of Alzheimer's disease, mice were treated with β-hydroxybutyric acid or a placebo. Compared to placebo-treated mice, β-hydroxybutyric acid-mice showed better performances in <a href="/wiki/Cognitive_test" title="Cognitive test">cognitive</a>/memory testing; lower brain levels of the pro-inflammatory cytokines <a href="/wiki/Interleukin-1_beta" class="mw-redirect" title="Interleukin-1 beta">interleukin-1 beta</a>, <a href="/wiki/Tumor_necrosis_factor-alpha" class="mw-redirect" title="Tumor necrosis factor-alpha">tumor necrosis factor-alpha</a>, and <a href="/wiki/Interleukin-6" class="mw-redirect" title="Interleukin-6">interleukin-6</a>; lower levels of brain amyloid-beta precursor protein and amyloid-β protein; and higher levels of <a href="/wiki/Neprilysin" title="Neprilysin">neprilysin</a>, an enzyme that degrades amyloid proteins and is essential to prevent Alzheimer's disease in mice (i.e., mice lacking a functional gene that encodes neprilysin develop Alzheimer's disease-like symptoms).<sup id="cite_ref-pmid36204834_13-13" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid31914599_42-1" class="reference"><a href="#cite_note-pmid31914599-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> In another study, 5xFAD mice who received β-hydroxybutyric acid subcutaneously for 28 days showed better cognitive functions, lower levels of Aβ peptide accumulation in the brain, and greater activation of microglia cells in the brain compared to placebo-treated mice. Furthermore, HCA<sub>2</sub> messenger RNA levels were increased in the brains of these mice during the period of active plaque deposition. (The postmortem brain tissues of patients with Alzheimer's disease also contained higher HCA<sub>2</sub> messenger RNA levels that those of individuals who did not have Alzheimer's disease.)<sup id="cite_ref-pmid31914599_42-2" class="reference"><a href="#cite_note-pmid31914599-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> In a third study, 5XFAD control mice that had normal levels of HCA<sub>2</sub> or had their <i>Hca2</i> gene knocked out were treated with a FDA-approved formulation of niacin, Niaspan. Niaspan-treated control mice had less brain <a href="/wiki/Neuron" title="Neuron">neuron</a> losses, fewer and smaller brain plaques, and better memory (as measured on a y-maze task test) than mice not treated with Niaspan: Niaspan did not produce these changes in <i>Hca2</i> gene knockout mice.<sup id="cite_ref-pmid35320002_43-1" class="reference"><a href="#cite_note-pmid35320002-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> These results indicate that HCA<sub>2</sub> suppresses the progression of Alzheimer's disease in a mouse model and support further studies with the ultimate goal of determining if HCA<sub>2</sub> activators would be a useful addition to the treatment of Alzheimer's disease.<sup id="cite_ref-pmid36204834_13-14" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid22435740_34-1" class="reference"><a href="#cite_note-pmid22435740-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid31914599_42-3" class="reference"><a href="#cite_note-pmid31914599-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid35320002_43-2" class="reference"><a href="#cite_note-pmid35320002-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Parkinson's_disease"><span id="Parkinson.27s_disease"></span>Parkinson's disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=9" title="Edit section: Parkinson's disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Individuals with Parkinson's disease develop progressively less control of their <a href="/wiki/Motor_control" title="Motor control">motor movements</a> in association with progressively greater losses of <a href="/wiki/Dopamine_neurons" class="mw-redirect" title="Dopamine neurons">dopamine neurons</a> within the <a href="/wiki/Pars_compacta" title="Pars compacta">pars compacta</a> subdivision of their brain's <a href="/wiki/Substantia_nigra" title="Substantia nigra">substantia nigra</a>. After longer times with the disease, individuals may also develop worsening <a href="/wiki/Cognition" title="Cognition">cognition</a> symptoms and, ultimately, <a href="/wiki/Parkinson%27s_disease_dementia" title="Parkinson's disease dementia">Parkinson's disease dementia</a>.<sup id="cite_ref-pmid32652199_44-0" class="reference"><a href="#cite_note-pmid32652199-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> Some studies suggest that HCA<sub>2</sub> may act to suppress this disease's progression. In a mouse model of Parkinson's disease, control male mice and <i>Hcar2</i> gene knockout male mice received lipopolysaccharide (an inflammation-inducing <a href="/wiki/Bacterial_toxin" class="mw-redirect" title="Bacterial toxin">bacterial toxin</a>) injections into the right substantia nigra of their brains and examined 28 days after the injections. Compared to control mice, <i>Hcar2</i> gene knockout mice evidenced greater injury to their dopamine neurons, severer motor deficits, and more inflammation as judged by the levels of three pro-inflammatory cytokines (i.e., interleukin-6, <a href="/wiki/Interleukin-1%CE%B2" class="mw-redirect" title="Interleukin-1β">interleukin-1β</a>, and tumor necrosis factor-α) in their midbrain tissues and <a href="/wiki/Serum_(blood)" title="Serum (blood)">serum</a>. Further studies examined mice that had their <i>Hcar2</i> gene knocked out in their microglia but not in other tissues. Following the lipopolysaccharide injection protocol just described, the mice were feed a niacin solution for 28 days. This regimen alleviated dopamine neuron injuries and motor deficits in control mice but not in mice constructed to have <i>Hcar2</i> gene knockout microglial cells.<sup id="cite_ref-pmid36991440_45-0" class="reference"><a href="#cite_note-pmid36991440-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> In the model of <a href="/wiki/MPTP#Contribution_of_MPTP_to_research_into_Parkinson's_disease" title="MPTP">MPTP</a>-induced Parkinson's disease, mice received <a href="/wiki/Intraperitoneal_injection" title="Intraperitoneal injection">intraperitoneal injections</a> of MPTP or a <a href="/wiki/Placebo" title="Placebo">placebo</a> (e.g., salt water) daily for 7 days followed by daily feeding (by <a href="/wiki/Gavage" class="mw-redirect" title="Gavage">gavage</a>) of a salt water placebo, butyric acid, or monomethyl fumarate for 14 days. Compared to mice not treated with MPTP, mice treated with MPTP followed by salt water developed defective motor functions as defined in three different tests, lower dopamine levels in their corpus striatum, activation of the microglia in their <a href="/wiki/Substantia_nigra" title="Substantia nigra">substantia nigra</a>, and evidence of systemic inflammation (i.e., increased serum levels of the pro-inflammatory cytokines, tumor necrosis factor-α and interleuken-6). Mice treated with MPTP followed by butyric acid or monomethyl fumarate were significantly protected from developing these changes. Further studies suggested that the activation of HCA<sub>2</sub> on microglial cells stimulated their change from a pro-inflammatory to anti-inflammatory <a href="/wiki/Phenotype" title="Phenotype">phenotype</a>.<sup id="cite_ref-pmid36235813_46-0" class="reference"><a href="#cite_note-pmid36235813-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> These results indicate that HCA<sub>2</sub> suppresses the inflammation, neuronal damage, and neurological symptoms in mouse Parkinson's disease models and suggest that agents activating this receptor may be of use in treating and therefore should be further studied in humans with this disease.<sup id="cite_ref-pmid36204834_13-15" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid36991440_45-1" class="reference"><a href="#cite_note-pmid36991440-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid36235813_46-1" class="reference"><a href="#cite_note-pmid36235813-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Multiple_sclerosis">Multiple sclerosis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=10" title="Edit section: Multiple sclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Multiple sclerosis is an <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune</a> <a href="/wiki/Demyelinating_disease" title="Demyelinating disease">demyelinating disease</a> in which an individual's immune system's causes an inflammation-based destruction of the <a href="/wiki/Myelin_sheath" class="mw-redirect" title="Myelin sheath">myelin sheath</a> surrounding <a href="/wiki/Neurons" class="mw-redirect" title="Neurons">neurons</a> in the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a>. This disrupts the afflicted neurons' functions and causes various neurological symptoms depending on which neurons are damaged.<sup id="cite_ref-pmid36204834_13-16" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> In a murine <a href="/wiki/Experimental_autoimmune_encephalomyelitis" title="Experimental autoimmune encephalomyelitis">experimental autoimmune encephalomyelitis</a> model of multiple sclerosis, mice taking oral dimethyl fumarate had less immune cell infiltration and demyelination in their spinal cords and improved motor function compared to mice not treated with dimethyl fumarate. These dimethyl fumarate-induced improvements did not occur in <i>Hcar2</i> gene knockout mice.<sup id="cite_ref-pmid36204834_13-17" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid24691444_47-0" class="reference"><a href="#cite_note-pmid24691444-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> Studies in lipopolysaccaride-treated <a href="/wiki/Cell_culture" title="Cell culture">cultured</a> murine microglial cells found that monomethyl fumarate switched the cells from a pro-inflammatory to an anti-inflammatory <a href="/wiki/Phenotype" title="Phenotype">phenotype</a>. Microglial cells pretreated with an antibody that binds to and thereby blocks activation of HCA<sub>2</sub> did not show these phenotypic changes. These studies indicate that HCA<sub>2</sub> acts to suppress the inflammation and thereby neurological symptoms in a mouse model of multiple sclerosis. In 2013, the <a href="/wiki/Federal_Drug_Administration" class="mw-redirect" title="Federal Drug Administration">Federal Drug Administration</a> approved dimethyl fumarate (trade name Tecfidera<sup id="cite_ref-pmid35569547_31-1" class="reference"><a href="#cite_note-pmid35569547-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup>) for the treatment of multiple sclerosis.<sup id="cite_ref-pmid21454438_5-3" class="reference"><a href="#cite_note-pmid21454438-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> Although it is now regarded as one of the front-line (i.e. first used) therapies for treating this disease, dimethyl fumarate's <a href="/wiki/Mechanism_of_action" title="Mechanism of action">mechanism of action</a>, including its impact on HCA<sub>2</sub> in human multiple sclerosis, has not yet been defined<sup id="cite_ref-pmid35569547_31-2" class="reference"><a href="#cite_note-pmid35569547-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> and needs to be study.<sup id="cite_ref-pmid36204834_13-18" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Pathological_pain">Pathological pain</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=11" title="Edit section: Pathological pain"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Pathologic pain is due to the abnormal activation of neurons in <a href="/wiki/Nav1.8" title="Nav1.8">pain signaling pathways</a>)<sup id="cite_ref-pmid36204834_13-19" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid32291648_48-0" class="reference"><a href="#cite_note-pmid32291648-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> For example, neurons in the <a href="/wiki/Vertebral_column" title="Vertebral column">vertebral column</a>'s <a href="/wiki/Posterior_grey_column" class="mw-redirect" title="Posterior grey column">posterior horn</a> of the <a href="/wiki/Spinal_cord" title="Spinal cord">spinal cord</a> are part of one pain signaling pathway. Excessive activation of these neurons caused by inflammation stimulates the production of pro-inflammatory cytokines (e.g., interleukin-2 and tumor necrosis factor-α) and persistent <a href="/wiki/Nociplastic_pain" title="Nociplastic pain">nociplastic pain</a>.<sup id="cite_ref-pmid32291648_48-1" class="reference"><a href="#cite_note-pmid32291648-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> Numerous studies in mice and rats have reported that β-hydroxybutyric acid, dimethyl fumarate, and MK-1903 have <a href="/wiki/Analgesic" title="Analgesic">analgesic</a> effects in models of thermal and mechanical hypersensitivity due to tibial bone fracture, <a href="/wiki/Intervertebral_disc" title="Intervertebral disc">intervertebral disc</a> degeneration, complete Freund's adjuvant-induced arthritis, <a href="/wiki/Systemic_lupus_erythematosus" class="mw-redirect" title="Systemic lupus erythematosus">systemic lupus erythematosus</a>, and chronic constriction of the <a href="/wiki/Sciatic_nerve" title="Sciatic nerve">sciatic nerve</a>.<sup id="cite_ref-pmid36204834_13-20" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> In the mouse model of pain induced by chronic constriction of the sciatic nerve, the pain-relieving effects of β-hydroxybutyric acid and dimethyl fumarate did not occur in <i>Hca2</i> <a href="/wiki/Gene_knockout" title="Gene knockout">gene knockout</a> mice.<sup id="cite_ref-pmid30085883_49-0" class="reference"><a href="#cite_note-pmid30085883-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> These results indicate that HCA<sub>2</sub> suppresses various types of pathological pain in mice and support studies to learn if it does so in humans.<sup id="cite_ref-pmid36204834_13-21" class="reference"><a href="#cite_note-pmid36204834-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Mastitis">Mastitis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=12" title="Edit section: Mastitis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Mastitis is an infection-related or sterile inflammation of breast tissue. In a murine model of <a href="/wiki/Mastitis" title="Mastitis">mastitis</a>, post-pregnant female mice drank niacin-containing or normal water for 26 days and then received lipopolysaccharide injections into the fourth pair of their <a href="/wiki/Mammary_glands" class="mw-redirect" title="Mammary glands">mammary glands</a>. The next day each mammary gland was examined. Mouse fed pure water had extensive inflammation of their lipopolysaccharide-injected mammary glands, elevated mammary gland levels of pro-inflammatory cytokines (i.e., interleukin-6, interleukin-1β, and tumor necrosis factor-α), severe structural abnormalities such as thickened walls around their breasts' milk-producing <a href="/wiki/Mammary_alveolus" title="Mammary alveolus">alveoli</a>, and breakdown of the blood-milk barrier which prevents uncontrolled exchange of components between the blood and alveolar milk. The mammary glands of lipopolysaccharide-injected, niacin-fed control mice but not niacin-fed <i>Hca2</i> gene knockout mice had far less of these changes. These results indicate that HCA<sub>2</sub> functions to suppress the inflammation and tissue injuries that develop in a mouse model of mastitis.<sup id="cite_ref-pmid34803497_20-2" class="reference"><a href="#cite_note-pmid34803497-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> HCA<sub>2</sub> may play a similar role in <a href="/wiki/Bovines" class="mw-redirect" title="Bovines">bovines</a>: dairy cows with mastitis that were fed niacin for 7 days showed decreases in their serum and milk levels of pro-inflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-6, and interleukin-1β) and fewer cells in their milk compared to cows with mastitis that were not treated with niacin. It was also noted that the mammary tissue levels of HCA<sub>2</sub> were higher in cows with than those without mastitis.<sup id="cite_ref-pmid32397071_50-0" class="reference"><a href="#cite_note-pmid32397071-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> Thus, HCA<sub>2</sub> may prove to be a target for treating mastitis in cows and might be useful to examine its roles in the in human mastitis.<sup id="cite_ref-pmid34803497_20-3" class="reference"><a href="#cite_note-pmid34803497-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid32397071_50-1" class="reference"><a href="#cite_note-pmid32397071-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Alcoholic_hepatitis">Alcoholic hepatitis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=13" title="Edit section: Alcoholic hepatitis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In a model of <a href="/wiki/Alcoholic_hepatitis" title="Alcoholic hepatitis">alcohol-induced hepatitis</a>, β-hydroxybutyric acid-treated mice showed less evidence of liver inflammation compared to control mice as indicated by their: <b>1)</b> lower <a href="/wiki/Blood_plasma" title="Blood plasma">plasma</a> levels of <a href="/wiki/Liver_function_tests#Alanine_transaminase" title="Liver function tests">alanine transaminase</a> (an enzyme released into the bloodstream by damaged liver cells); <b>2)</b> less liver <a href="/wiki/Steatosis" title="Steatosis">steatosis</a> (i.e., lower levels of liver fat); and <b>3)</b> lower numbers of inflammation-promoting <a href="/wiki/Neutrophils" class="mw-redirect" title="Neutrophils">neutrophils</a>, higher numbers of inflammation-suppressing <a href="/wiki/Macrophages#Subtypes" class="mw-redirect" title="Macrophages">M2 macrophages</a>, and higher levels of <a href="/wiki/Messenger_RNA" title="Messenger RNA">messenger RNA</a> encoding an inflammation-suppressing cytokine, <a href="/wiki/Interleukin_10" title="Interleukin 10">IL-10</a>, in their livers. The inflammation-reducing effects of β-hydroxybutyric acid did not occur in <i>Hcar2</i> gene knockout mice. In human studies, the concentration of β-hydroxybutyric acid in the livers of ten patients with alcoholic hepatitis was significantly lower than that of normal individuals. These findings indicate that HCA<sub>2</sub> acts to reduce the severity of alcohol-induced hepatitis in mice and suggest that it may also do so, and therefore should be further studied, in humans.<sup id="cite_ref-pmid29705237_21-1" class="reference"><a href="#cite_note-pmid29705237-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Inflammatory_bowel_disease_and_colon_cancer">Inflammatory bowel disease and colon cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=14" title="Edit section: Inflammatory bowel disease and colon cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Inflammatory_bowel_diseases" class="mw-redirect" title="Inflammatory bowel diseases">Inflammatory bowel diseases</a>, i.e., <a href="/wiki/Ulcerative_colitis" title="Ulcerative colitis">ulcerative colitis</a> and <a href="/wiki/Crohn%27s_disease" title="Crohn's disease">Crohn's disease</a>, are chronic inflammatory diseases of the <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal tract</a> that can progress to <a href="/wiki/Colon_cancer" class="mw-redirect" title="Colon cancer">colon cancer</a>.<sup id="cite_ref-pmid24412617_22-1" class="reference"><a href="#cite_note-pmid24412617-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> Colon cancer, even if not preceded by an inflammatory bowel disease, commonly shows the presence of the inflammation response that is mounted to fight invading intestinal <a href="/wiki/Microorganisms" class="mw-redirect" title="Microorganisms">microorganisms</a>. In a murine model of colitis, rats were given niacin or water for 2 weeks, given daily <a href="/wiki/Rectal" class="mw-redirect" title="Rectal">rectal</a> injections of the colitis-inducing agent, <a href="/wiki/Iodoacetamide" title="Iodoacetamide">iodoacetamide</a>, and sacrificed on day 15. Compared to water-treated rats, niacin-treated rats developed milder colitis as defined by less declines in body weight, less declines in colon weights, and less rises in colon tissue levels of <a href="/wiki/Myeloperoxidase" title="Myeloperoxidase">myeloperoxidase</a>, an indicator of inflammatory cell (i.e. <a href="/wiki/Polymorphonuclear_leukocytes" class="mw-redirect" title="Polymorphonuclear leukocytes">polymorphonuclear leukocytes</a>) infiltration. In a murine model of colitis leading to colon cancer, mice were treated with dextran sulfate sodium to produce colitis and an intraperitoneal injection of <a href="/wiki/Azoxymethane" title="Azoxymethane">azoxymethane</a>, a colon cancer-causing <a href="/wiki/Carcinogen" title="Carcinogen">carcinogen</a>. In this Apc<sup>Min/+</sup> murine model: <b>1)</b> mice fed a diet that greatly reduced the levels of butyric acid in the colon developed colitis and numerous potentially pre-cancerous colon <a href="/wiki/Polyp_(medicine)" title="Polyp (medicine)">polyps</a>; <b>2)</b> mice fed a normal diet had less of these changes; and <b>3)</b> niacin treatment of mice fed the butyric acid-reducing diet suppressed these changes but did not do so in <i>Hcar2</i> gene knockout mice on the butyric acid-reducing diet.<sup id="cite_ref-pmid24412617_22-2" class="reference"><a href="#cite_note-pmid24412617-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> Thus, HCA<sub>2</sub> acts to inhibit colitis in rat as well as mouse models of colitis and in the mouse ulcerative colitis model reduced the formation of potentially pre-cancerous polyps.<sup id="cite_ref-pmid24412617_22-3" class="reference"><a href="#cite_note-pmid24412617-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> In human studies, the levels of <a href="/wiki/Messenger_RNA" title="Messenger RNA">messenger RNA</a> encoding HCA<sub>2</sub> in 18 individuals with colon cancer were far lower in their cancers than their normal colon tissues and were also lower in 10 human colon cancer <a href="/wiki/Cell_line" class="mw-redirect" title="Cell line">cell lines</a> than 2 human non-cancerous colon cell lines. (HCA<sub>3</sub> messenger RNA levels were also lower in the colon cancer than non-cancerous colon tissue of the patients.) Furthermore, individuals who have inflammatory bowel disease and consume a diet that increases their levels of β-hydroxybutyric and butyric acid have been suggested to show clinical improvements in their disease and a reduced rate of it progressing to colon cancer.<sup id="cite_ref-pmid33897470_26-1" class="reference"><a href="#cite_note-pmid33897470-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> These findings suggest that human colon cancers not preceded by an inflammatory bowel disease are associated with reductions in the expression of HCA<sub>2</sub> (and HCA<sub>3</sub>) due to <a href="/wiki/Gene_silencing" title="Gene silencing">gene silencing</a>, that the reductions of HCA<sub>2</sub> (and/or HCA<sub>3</sub>) may be involved in the development and/or progression of these cancers.<sup id="cite_ref-pmid19276343_51-0" class="reference"><a href="#cite_note-pmid19276343-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid33631190_52-0" class="reference"><a href="#cite_note-pmid33631190-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> and that HCA<sub>2</sub> may act to suppress human ulcerative colitis as well as its progression to colon cancer.<sup id="cite_ref-pmid33897470_26-2" class="reference"><a href="#cite_note-pmid33897470-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Other_diseases">Other diseases</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=15" title="Edit section: Other diseases"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Activators of HCA<sub>2</sub> have been shown to suppress the inflammation and severity of disease in two other animal models. However, these studies did not examine <i>Hca2</i> gene knockout/knockdown animals. These models are for <a href="/wiki/Psoriasis" title="Psoriasis">psoriasis</a><sup id="cite_ref-pmid37004600_23-2" class="reference"><a href="#cite_note-pmid37004600-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> and brain tissue inflammation, injury, and behavioral abnormalities caused by <a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">alcohol</a>.<sup id="cite_ref-pmid36709599_24-2" class="reference"><a href="#cite_note-pmid36709599-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Hydroxycarboxylic_acid_receptor_2&action=edit&section=16" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 33em;"> <ol class="references"> <li id="cite_note-refGRCh38Ensembl-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-refGRCh38Ensembl_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><a rel="nofollow" class="external text" href="http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000182782">GRCh38: Ensembl release 89: ENSG00000182782</a> – <a href="/wiki/Ensembl_genome_database_project" title="Ensembl genome database project">Ensembl</a>, May 2017</span> </li> <li id="cite_note-refGRCm38Ensembl-2"><span class="mw-cite-backlink">^ <a href="#cite_ref-refGRCm38Ensembl_2-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-refGRCm38Ensembl_2-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-refGRCm38Ensembl_2-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><a rel="nofollow" class="external text" href="http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000045502">GRCm38: Ensembl release 89: ENSMUSG00000045502</a> – <a href="/wiki/Ensembl_genome_database_project" title="Ensembl genome database project">Ensembl</a>, May 2017</span> </li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="#cite_ref-3">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration 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class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Class_A:_Rhodopsin-like" style="font-size:114%;margin:0 4em"><a href="/wiki/Rhodopsin-like_receptors" title="Rhodopsin-like receptors">Class A</a>: <a href="/wiki/Rhodopsin" title="Rhodopsin">Rhodopsin</a>-like</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Neurotransmitter_receptor" title="Neurotransmitter receptor">Neurotransmitter</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Adrenergic_receptor" title="Adrenergic receptor">Adrenergic</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Alpha-1_adrenergic_receptor" title="Alpha-1 adrenergic receptor">α1</a> (<a href="/wiki/Alpha-1A_adrenergic_receptor" title="Alpha-1A adrenergic receptor">A</a></li> <li><a href="/wiki/Alpha-1B_adrenergic_receptor" title="Alpha-1B adrenergic receptor">B</a></li> <li><a href="/wiki/Alpha-1D_adrenergic_receptor" title="Alpha-1D adrenergic receptor">D</a>)</li> <li><a href="/wiki/Alpha-2_adrenergic_receptor" title="Alpha-2 adrenergic receptor">α2</a> (<a href="/wiki/Alpha-2A_adrenergic_receptor" title="Alpha-2A adrenergic receptor">A</a></li> <li><a href="/wiki/Alpha-2B_adrenergic_receptor" title="Alpha-2B adrenergic receptor">B</a></li> <li><a href="/wiki/Alpha-2C_adrenergic_receptor" title="Alpha-2C adrenergic receptor">C</a>)</li> <li><a href="/wiki/Beta-1_adrenergic_receptor" title="Beta-1 adrenergic receptor">β1</a></li> <li><a href="/wiki/Beta-2_adrenergic_receptor" title="Beta-2 adrenergic receptor">β2</a></li> <li><a href="/wiki/Beta-3_adrenergic_receptor" title="Beta-3 adrenergic receptor">β3</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Purinergic_receptor" title="Purinergic receptor">Purinergic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adenosine_receptor" title="Adenosine receptor">Adenosine</a> (<a href="/wiki/Adenosine_A1_receptor" title="Adenosine A1 receptor">A1</a></li> <li><a href="/wiki/Adenosine_A2A_receptor" title="Adenosine A2A receptor">A2A</a></li> <li><a href="/wiki/Adenosine_A2B_receptor" title="Adenosine A2B receptor">A2B</a></li> <li><a href="/wiki/Adenosine_A3_receptor" title="Adenosine A3 receptor">A3</a>)</li> <li><a href="/wiki/P2Y_receptor" title="P2Y receptor">P2Y</a> (<a href="/wiki/P2RY1" title="P2RY1">1</a></li> <li><a href="/wiki/P2RY2" title="P2RY2">2</a></li> <li><a href="/wiki/P2RY4" title="P2RY4">4</a></li> <li><a href="/wiki/LPAR6" title="LPAR6">5</a></li> <li><a href="/wiki/P2RY6" title="P2RY6">6</a></li> <li><a href="/wiki/P2RY8" title="P2RY8">8</a></li> <li><a href="/wiki/GPR23" class="mw-redirect" title="GPR23">9</a></li> <li><a href="/wiki/P2RY10" title="P2RY10">10</a></li> <li><a href="/wiki/P2RY11" title="P2RY11">11</a></li> <li><a href="/wiki/P2Y12" title="P2Y12">12</a></li> <li><a href="/wiki/P2RY13" title="P2RY13">13</a></li> <li><a href="/wiki/P2RY14" title="P2RY14">14</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/5-HT_receptor" title="5-HT receptor">Serotonin</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>(all but <a href="/wiki/5-HT3_receptor" title="5-HT3 receptor">5-HT3</a>)</i> <a href="/wiki/5-HT1_receptor" title="5-HT1 receptor">5-HT1</a> (<a href="/wiki/5-HT1A_receptor" title="5-HT1A receptor">A</a></li> <li><a href="/wiki/5-HT1B_receptor" title="5-HT1B receptor">B</a></li> <li><a href="/wiki/5-HT1D_receptor" title="5-HT1D receptor">D</a></li> <li><a href="/wiki/5-HT1E_receptor" title="5-HT1E receptor">E</a></li> <li><a href="/wiki/5-HT1F_receptor" title="5-HT1F receptor">F</a>)</li> <li><a href="/wiki/5-HT2_receptor" title="5-HT2 receptor">5-HT2</a> (<a href="/wiki/5-HT2A_receptor" title="5-HT2A receptor">A</a></li> <li><a href="/wiki/5-HT2B_receptor" title="5-HT2B receptor">B</a></li> <li><a href="/wiki/5-HT2C_receptor" title="5-HT2C receptor">C</a>)</li> <li><i>5-HT</i> (<a href="/wiki/5-HT4_receptor" title="5-HT4 receptor">4</a></li> <li><a href="/wiki/5-HT5A_receptor" title="5-HT5A receptor">5A</a></li> <li><a href="/wiki/5-HT6_receptor" title="5-HT6 receptor">6</a></li> <li><a href="/wiki/5-HT7_receptor" title="5-HT7 receptor">7</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Muscarinic_acetylcholine_receptor" title="Muscarinic acetylcholine receptor">Acetylcholine</a> (<a href="/wiki/Muscarinic_acetylcholine_receptor_M1" title="Muscarinic acetylcholine receptor M1">M1</a></li> <li><a href="/wiki/Muscarinic_acetylcholine_receptor_M2" title="Muscarinic acetylcholine receptor M2">M2</a></li> <li><a href="/wiki/Muscarinic_acetylcholine_receptor_M3" title="Muscarinic acetylcholine receptor M3">M3</a></li> <li><a href="/wiki/Muscarinic_acetylcholine_receptor_M4" title="Muscarinic acetylcholine receptor M4">M4</a></li> <li><a href="/wiki/Muscarinic_acetylcholine_receptor_M5" title="Muscarinic acetylcholine receptor M5">M5</a>)</li> <li><a href="/wiki/Dopamine_receptor" title="Dopamine receptor">Dopamine</a> <ul><li><a href="/wiki/Dopamine_receptor_D1" title="Dopamine receptor D1">D1</a></li> <li><a href="/wiki/Dopamine_receptor_D2" title="Dopamine receptor D2">D2</a></li> <li><a href="/wiki/Dopamine_receptor_D3" title="Dopamine receptor D3">D3</a></li> <li><a href="/wiki/Dopamine_receptor_D4" title="Dopamine receptor D4">D4</a></li> <li><a href="/wiki/Dopamine_receptor_D5" title="Dopamine receptor D5">D5</a></li></ul></li> <li><a href="/wiki/GHB_receptor" title="GHB receptor">GHB receptor</a></li> <li><a href="/wiki/Histamine_receptor" title="Histamine receptor">Histamine</a> <ul><li><a href="/wiki/Histamine_H1_receptor" title="Histamine H1 receptor">H1</a></li> <li><a href="/wiki/Histamine_H2_receptor" title="Histamine H2 receptor">H2</a></li> <li><a href="/wiki/Histamine_H3_receptor" title="Histamine H3 receptor">H3</a></li> <li><a href="/wiki/Histamine_H4_receptor" title="Histamine H4 receptor">H4</a></li></ul></li> <li><a href="/wiki/Melatonin_receptor" title="Melatonin receptor">Melatonin</a> (<a href="/wiki/Melatonin_receptor_1A" title="Melatonin receptor 1A">1A</a></li> <li><a href="/wiki/Melatonin_receptor_1B" title="Melatonin receptor 1B">1B</a></li> <li><a href="/wiki/Melatonin_receptor_1C" title="Melatonin receptor 1C">1C</a>)</li> <li><a href="/wiki/Trace_amine-associated_receptor" title="Trace amine-associated receptor">TAAR</a> (<a href="/wiki/TAAR1" title="TAAR1">1</a></li> <li><a href="/wiki/TAAR2" title="TAAR2">2</a></li> <li><a href="/wiki/TAAR5" title="TAAR5">5</a></li> <li><a href="/wiki/TAAR6" title="TAAR6">6</a></li> <li><a href="/wiki/TAAR8" title="TAAR8">8</a></li> <li><a href="/wiki/TAAR9" title="TAAR9">9</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Metabolites and<br />signaling molecules</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Eicosanoid_receptor" title="Eicosanoid receptor">Eicosanoid</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>CysLT</i> (<a href="/wiki/Cysteinyl_leukotriene_receptor_1" title="Cysteinyl leukotriene receptor 1">1</a></li> <li><a href="/wiki/Cysteinyl_leukotriene_receptor_2" title="Cysteinyl leukotriene receptor 2">2</a>)</li> <li><a href="/wiki/Leukotriene_B4" title="Leukotriene B4">LTB4</a> <ul><li><a href="/wiki/Leukotriene_B4_receptor" title="Leukotriene B4 receptor">1</a></li> <li><a href="/wiki/Leukotriene_B4_receptor_2" title="Leukotriene B4 receptor 2">2</a></li></ul></li> <li><a href="/wiki/Formyl_peptide_receptor_2" title="Formyl peptide receptor 2"> FPRL1</a></li> <li><a href="/wiki/Oxoeicosanoid_receptor_1" title="Oxoeicosanoid receptor 1">OXE</a></li> <li><a href="/wiki/Prostaglandin_receptor" title="Prostaglandin receptor">Prostaglandin</a> <ul><li><i>DP</i> (<a href="/wiki/Prostaglandin_D2_receptor" title="Prostaglandin D2 receptor">1</a></li> <li><a href="/wiki/GPR44" class="mw-redirect" title="GPR44">2</a>), <i>EP</i> (<a href="/wiki/EP1_receptor" class="mw-redirect" title="EP1 receptor">1</a></li> <li><a href="/wiki/Prostaglandin_E2_receptor" title="Prostaglandin E2 receptor">2</a></li> <li><a href="/wiki/Prostaglandin_E_receptor_3" class="mw-redirect" title="Prostaglandin E receptor 3">3</a></li> <li><a href="/wiki/EP4_receptor" class="mw-redirect" title="EP4 receptor">4</a>), <a href="/wiki/Prostaglandin_F_receptor" title="Prostaglandin F receptor">FP</a></li></ul></li> <li><a href="/wiki/Prostacyclin_receptor" title="Prostacyclin receptor">Prostacyclin</a></li> <li><a href="/wiki/Thromboxane_receptor" title="Thromboxane receptor">Thromboxane</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/G_protein-coupled_bile_acid_receptor" title="G protein-coupled bile acid receptor">Bile acid</a></li> <li><a href="/wiki/Cannabinoid_receptor" title="Cannabinoid receptor">Cannabinoid</a> (<a href="/wiki/Cannabinoid_receptor_type_1" class="mw-redirect" title="Cannabinoid receptor type 1">CB1</a></li> <li><a href="/wiki/Cannabinoid_receptor_type_2" class="mw-redirect" title="Cannabinoid receptor type 2">CB2</a>, <i>GPR</i> (<a href="/wiki/GPR18" class="mw-redirect" title="GPR18">18</a></li> <li><a href="/wiki/GPR55" title="GPR55">55</a></li> <li><a href="/wiki/GPR119" title="GPR119">119</a>))</li> <li><a href="/wiki/GPR183" title="GPR183">EBI2</a></li> <li><a href="/wiki/GPER" title="GPER">Estrogen</a></li> <li><a href="/wiki/Free_fatty_acid_receptor" title="Free fatty acid receptor">Free fatty acid</a> (<a href="/wiki/Free_fatty_acid_receptor_1" title="Free fatty acid receptor 1">1</a></li> <li><a href="/wiki/Free_fatty_acid_receptor_2" title="Free fatty acid receptor 2">2</a></li> <li><a href="/wiki/Free_fatty_acid_receptor_3" title="Free fatty acid receptor 3">3</a></li> <li><a href="/wiki/GPR42" title="GPR42">4</a>)</li> <li><a href="/wiki/Hydroxycarboxylic_acid_receptor" title="Hydroxycarboxylic acid receptor">Hydroxycarboxylic acids</a> <ul><li><a href="/wiki/Hydroxycarboxylic_acid_receptor_1" title="Hydroxycarboxylic acid receptor 1">1</a></li> <li><a class="mw-selflink selflink">2</a></li> <li><a href="/wiki/Hydroxycarboxylic_acid_receptor_3" title="Hydroxycarboxylic acid receptor 3">3</a></li></ul></li> <li><a href="/wiki/Lysophosphatidic_acid" title="Lysophosphatidic acid">Lysophosphatidic acid</a> (<a href="/wiki/LPAR1" title="LPAR1">1</a></li> <li><a href="/wiki/LPAR2" title="LPAR2">2</a></li> <li><a href="/wiki/LPAR3" title="LPAR3">3</a></li> <li><a href="/wiki/LPAR4" title="LPAR4">4</a></li> <li><a href="/wiki/LPAR5" title="LPAR5">5</a></li> <li><a href="/wiki/LPAR6" title="LPAR6">6</a>)</li> <li><a href="/wiki/Lysophospholipid_receptor" title="Lysophospholipid receptor">Lysophospholipid</a> (<a href="/wiki/S1PR1" title="S1PR1">1</a></li> <li><a href="/wiki/LPAR1" title="LPAR1">2</a></li> <li><a href="/wiki/S1PR3" title="S1PR3">3</a></li> <li><a href="/wiki/LPAR2" title="LPAR2">4</a></li> <li><a href="/wiki/S1PR2" title="S1PR2">5</a></li> <li><a href="/wiki/S1PR4" title="S1PR4">6</a></li> <li><a href="/wiki/LPAR3" title="LPAR3">7</a></li> <li><a href="/wiki/S1PR5" title="S1PR5">8</a>)</li> <li><a href="/wiki/OXGR1" title="OXGR1">Oxoglutarate</a></li> <li><a href="/wiki/Platelet-activating_factor_receptor" title="Platelet-activating factor receptor">PAF</a></li> <li><a href="/wiki/Sphingosine-1-phosphate" title="Sphingosine-1-phosphate">Sphingosine-1-phosphate</a> (<a href="/wiki/S1PR1" title="S1PR1">1</a></li> <li><a href="/wiki/S1PR2" title="S1PR2">2</a></li> <li><a href="/wiki/S1PR3" title="S1PR3">3</a></li> <li><a href="/wiki/S1PR4" title="S1PR4">4</a></li> <li><a href="/wiki/S1PR5" title="S1PR5">5</a>)</li> <li><a href="/wiki/SUCNR1" title="SUCNR1">Succinate</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Peptide</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/GPCR_neuropeptide_receptor" title="GPCR neuropeptide receptor">Neuropeptide</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Neuropeptide_B/W_receptor" title="Neuropeptide B/W receptor">B/W</a> (<a href="/wiki/Neuropeptides_B/W_receptor_1" title="Neuropeptides B/W receptor 1">1</a></li> <li><a href="/wiki/Neuropeptides_B/W_receptor_2" title="Neuropeptides B/W receptor 2">2</a>)</li> <li><a href="/wiki/Neuropeptide_FF_receptor" title="Neuropeptide FF receptor">FF</a> (<a href="/wiki/Neuropeptide_FF_receptor_1" title="Neuropeptide FF receptor 1">1</a></li> <li><a href="/wiki/Neuropeptide_FF_receptor_2" title="Neuropeptide FF receptor 2">2</a>)</li> <li><a href="/wiki/Neuropeptide_S_receptor" title="Neuropeptide S receptor">S</a></li> <li><a href="/wiki/Neuropeptide_Y_receptor" title="Neuropeptide Y receptor">Y</a> (<a href="/wiki/Neuropeptide_Y_receptor_Y1" title="Neuropeptide Y receptor Y1">1</a></li> <li><a href="/wiki/Neuropeptide_Y_receptor_Y2" title="Neuropeptide Y receptor Y2">2</a></li> <li><a href="/wiki/Pancreatic_polypeptide_receptor_1" title="Pancreatic polypeptide receptor 1">4</a></li> <li><a href="/wiki/Neuropeptide_Y_receptor_Y5" title="Neuropeptide Y receptor Y5">5</a>)</li> <li><i>Neuromedin</i> (<a href="/wiki/Neuromedin_B_receptor" title="Neuromedin B receptor">B</a></li> <li><a href="/wiki/Neuromedin_U_receptor" title="Neuromedin U receptor">U</a> (<a href="/wiki/Neuromedin_U_receptor_1" title="Neuromedin U receptor 1">1</a></li> <li><a href="/wiki/Neuromedin_U_receptor_2" title="Neuromedin U receptor 2">2</a>))</li> <li><a href="/wiki/Neurotensin_receptor" title="Neurotensin receptor">Neurotensin</a> (<a href="/wiki/Neurotensin_receptor_1" title="Neurotensin receptor 1">1</a></li> <li><a href="/wiki/Neurotensin_receptor_2" title="Neurotensin receptor 2">2</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anaphylatoxin_receptors" title="Anaphylatoxin receptors">Anaphylatoxin</a> (<a href="/wiki/C3a_receptor" title="C3a receptor">C3a</a></li> <li>C5a (<a href="/wiki/C5a_receptor" title="C5a receptor">1</a></li> <li><a href="/wiki/C5AR2" title="C5AR2">2</a>))</li> <li><a href="/wiki/Angiotensin_receptor" class="mw-redirect" title="Angiotensin receptor">Angiotensin</a> (<a href="/wiki/Angiotensin_II_receptor_type_1" title="Angiotensin II receptor type 1">1</a></li> <li><a href="/wiki/Angiotensin_II_receptor_type_2" title="Angiotensin II receptor type 2">2</a>)</li> <li><a href="/wiki/Apelin_receptor" title="Apelin receptor">Apelin</a></li> <li><a href="/wiki/Bombesin_receptor" title="Bombesin receptor">Bombesin</a> <ul><li><a href="/wiki/Bombesin-like_receptor_3" title="Bombesin-like receptor 3">BRS3</a></li> <li><a href="/wiki/Gastrin-releasing_peptide_receptor" title="Gastrin-releasing peptide receptor">GRPR</a></li> <li><a href="/wiki/Neuromedin_B_receptor" title="Neuromedin B receptor">NMBR</a>)</li> <li><a href="/wiki/Bradykinin_receptor" title="Bradykinin receptor">Bradykinin</a> (<a href="/wiki/Bradykinin_receptor_B1" title="Bradykinin receptor B1">B1</a></li> <li><a href="/wiki/Bradykinin_receptor_B2" title="Bradykinin receptor B2">B2</a>)</li></ul></li> <li><a href="/wiki/Chemokine_receptor" title="Chemokine receptor">Chemokine</a></li> <li><a href="/wiki/Cholecystokinin_receptor" title="Cholecystokinin receptor">Cholecystokinin</a> (<a href="/wiki/Cholecystokinin_A_receptor" title="Cholecystokinin A receptor">A</a></li> <li><a href="/wiki/Cholecystokinin_B_receptor" title="Cholecystokinin B receptor">B</a>)</li> <li><a href="/wiki/Endothelin_receptor" title="Endothelin receptor">Endothelin</a> <ul><li><a href="/wiki/Endothelin_A_receptor" title="Endothelin A receptor">A</a></li> <li><a href="/wiki/Endothelin_B_receptor" class="mw-redirect" title="Endothelin B receptor">B</a></li></ul></li> <li><a href="/wiki/Formyl_peptide_receptor" title="Formyl peptide receptor">Formyl peptide</a> (<a href="/wiki/Formyl_peptide_receptor_1" title="Formyl peptide receptor 1">1</a></li> <li><a href="/wiki/Formyl_peptide_receptor_2" title="Formyl peptide receptor 2">2</a></li> <li><a href="/wiki/Formyl_peptide_receptor_3" title="Formyl peptide receptor 3">3</a>)</li> <li><a href="/wiki/Follicle-stimulating_hormone_receptor" title="Follicle-stimulating hormone receptor">FSH</a></li> <li><a href="/wiki/Galanin_receptor" title="Galanin receptor">Galanin</a> (<a href="/wiki/Galanin_receptor_1" title="Galanin receptor 1">1</a></li> <li><a href="/wiki/Galanin_receptor_2" title="Galanin receptor 2">2</a></li> <li><a href="/wiki/Galanin_receptor_3" title="Galanin receptor 3">3</a>)</li> <li><a href="/wiki/Gonadotropin-releasing_hormone_receptor" title="Gonadotropin-releasing hormone receptor">Gonadotropin-releasing hormone</a> (<a href="/wiki/GNRHR" title="GNRHR">1</a></li> <li><a href="/wiki/GNRHR2" title="GNRHR2">2</a>)</li> <li><a href="/wiki/Growth_hormone_secretagogue_receptor" title="Growth hormone secretagogue receptor">Ghrelin</a></li> <li><a href="/wiki/KiSS1-derived_peptide_receptor" title="KiSS1-derived peptide receptor"> Kisspeptin</a></li> <li><a href="/wiki/Luteinizing_hormone/choriogonadotropin_receptor" title="Luteinizing hormone/choriogonadotropin receptor">Luteinizing hormone/choriogonadotropin</a></li> <li><a href="/wiki/MAS1_oncogene" title="MAS1 oncogene">MAS</a> (<a href="/wiki/MAS1" title="MAS1">1</a></li> <li><a href="/wiki/MAS1L" title="MAS1L">1L</a></li> <li><a href="/wiki/MRGPRD" title="MRGPRD">D</a></li> <li><a href="/wiki/MRGPRE" title="MRGPRE">E</a></li> <li><a href="/wiki/MRGPRF" title="MRGPRF">F</a></li> <li><a href="/wiki/MRGPRG" title="MRGPRG">G</a></li> <li><a href="/wiki/MRGPRX1" title="MRGPRX1">X1</a></li> <li><a href="/wiki/MRGPRX2" title="MRGPRX2">X2</a></li> <li><a href="/wiki/MRGPRX3" title="MRGPRX3">X3</a></li> <li><a href="/wiki/MRGPRX4" title="MRGPRX4">X4</a>)</li> <li><a href="/wiki/Melanocortin_receptor" title="Melanocortin receptor">Melanocortin</a> (<a href="/wiki/Melanocortin_1_receptor" title="Melanocortin 1 receptor">1</a></li> <li><a href="/wiki/ACTH_receptor" title="ACTH receptor">2</a></li> <li><a href="/wiki/Melanocortin_3_receptor" title="Melanocortin 3 receptor">3</a></li> <li><a href="/wiki/Melanocortin_4_receptor" title="Melanocortin 4 receptor">4</a></li> <li><a href="/wiki/Melanocortin_5_receptor" title="Melanocortin 5 receptor">5</a>)</li> <li><a href="/wiki/Melanin-concentrating_hormone_receptor" title="Melanin-concentrating hormone receptor">MCHR</a> (<a href="/wiki/Melanin-concentrating_hormone_receptor_1" title="Melanin-concentrating hormone receptor 1">1</a></li> <li><a href="/wiki/Melanin-concentrating_hormone_receptor_2" title="Melanin-concentrating hormone receptor 2">2</a>)</li> <li><a href="/wiki/Motilin_receptor" title="Motilin receptor">Motilin</a></li> <li><a href="/wiki/Opioid_receptor" title="Opioid receptor">Opioid</a> (<a href="/wiki/%CE%94-opioid_receptor" title="Δ-opioid receptor">Delta</a></li> <li><a href="/wiki/%CE%9A-opioid_receptor" title="Κ-opioid receptor">Kappa</a></li> <li><a href="/wiki/%CE%9C-opioid_receptor" title="Μ-opioid receptor">Mu</a></li> <li><a href="/wiki/Nociceptin_receptor" title="Nociceptin receptor">Nociceptin</a> & <a href="/wiki/OGFr" title="OGFr">Zeta</a>, but not <a href="/wiki/Sigma_receptor" title="Sigma receptor">Sigma</a>)</li> <li><a href="/wiki/Orexin_receptor" title="Orexin receptor">Orexin</a> (<a href="/wiki/Hypocretin_(orexin)_receptor_1" title="Hypocretin (orexin) receptor 1">1</a></li> <li><a href="/wiki/Hypocretin_(orexin)_receptor_2" title="Hypocretin (orexin) receptor 2">2</a>)</li> <li><a href="/wiki/Oxytocin_receptor" title="Oxytocin receptor">Oxytocin</a></li> <li><a href="/wiki/Prokineticin_receptor" title="Prokineticin receptor">Prokineticin</a> (<a href="/wiki/Prokineticin_receptor_1" title="Prokineticin receptor 1">1</a></li> <li><a href="/wiki/Prokineticin_receptor_2" title="Prokineticin receptor 2">2</a>)</li> <li><a href="/wiki/Prolactin-releasing_peptide_receptor" title="Prolactin-releasing peptide receptor">Prolactin-releasing peptide</a></li> <li><a href="/wiki/Relaxin_receptor" title="Relaxin receptor">Relaxin</a> (<a href="/wiki/Relaxin/insulin-like_family_peptide_receptor_1" title="Relaxin/insulin-like family peptide receptor 1">1</a></li> <li><a href="/wiki/Relaxin/insulin-like_family_peptide_receptor_2" title="Relaxin/insulin-like family peptide receptor 2">2</a></li> <li><a href="/wiki/Relaxin/insulin-like_family_peptide_receptor_3" title="Relaxin/insulin-like family peptide receptor 3">3</a></li> <li><a href="/wiki/Relaxin/insulin-like_family_peptide_receptor_4" title="Relaxin/insulin-like family peptide receptor 4">4</a>)</li> <li><a href="/wiki/Somatostatin_receptor" title="Somatostatin receptor">Somatostatin</a> (<a href="/wiki/Somatostatin_receptor_1" title="Somatostatin receptor 1">1</a></li> <li><a href="/wiki/Somatostatin_receptor_2" title="Somatostatin receptor 2">2</a></li> <li><a href="/wiki/Somatostatin_receptor_3" title="Somatostatin receptor 3">3</a></li> <li><a href="/wiki/Somatostatin_receptor_4" title="Somatostatin receptor 4">4</a></li> <li><a href="/wiki/Somatostatin_receptor_5" title="Somatostatin receptor 5">5</a>)</li> <li><a href="/wiki/Tachykinin_receptor" title="Tachykinin receptor">Tachykinin</a> (<a href="/wiki/Tachykinin_receptor_1" title="Tachykinin receptor 1">1</a></li> <li><a href="/wiki/Tachykinin_receptor_2" title="Tachykinin receptor 2">2</a></li> <li><a href="/wiki/Tachykinin_receptor_3" title="Tachykinin receptor 3">3</a>)</li> <li><a href="/wiki/Thyrotropin_receptor" title="Thyrotropin receptor">Thyrotropin</a></li> <li><a href="/wiki/Thyrotropin-releasing_hormone_receptor" title="Thyrotropin-releasing hormone receptor">Thyrotropin-releasing hormone</a></li> <li><a href="/wiki/Urotensin-II_receptor" title="Urotensin-II receptor">Urotensin-II</a></li> <li><a href="/wiki/Vasopressin_receptor" title="Vasopressin receptor">Vasopressin</a> (<a href="/wiki/Arginine_vasopressin_receptor_1A" class="mw-redirect" title="Arginine vasopressin receptor 1A">1A</a></li> <li><a href="/wiki/Arginine_vasopressin_receptor_1B" class="mw-redirect" title="Arginine vasopressin receptor 1B">1B</a></li> <li><a href="/wiki/Arginine_vasopressin_receptor_2" class="mw-redirect" title="Arginine vasopressin receptor 2">2</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;">Miscellaneous</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Taste_receptor" title="Taste receptor">Taste</a>, bitter</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>TAS2R</i> <ul><li><a href="/wiki/TAS2R1" title="TAS2R1">1</a></li> <li><a href="/wiki/TAS2R3" title="TAS2R3">3</a></li> <li><a href="/wiki/TAS2R4" title="TAS2R4">4</a></li> <li><a href="/wiki/TAS2R5" title="TAS2R5">5</a></li> <li><a href="/wiki/TAS2R7" title="TAS2R7">7</a></li> <li><a href="/wiki/TAS2R8" title="TAS2R8">8</a></li> <li><a href="/wiki/TAS2R9" title="TAS2R9">9</a></li> <li><a href="/wiki/TAS2R10" title="TAS2R10">10</a></li> <li><a href="/wiki/TAS2R13" title="TAS2R13">13</a></li> <li><a href="/wiki/TAS2R14" title="TAS2R14">14</a></li> <li><a href="/wiki/TAS2R16" title="TAS2R16">16</a></li> <li><a href="/wiki/TAS2R19" title="TAS2R19">19</a></li> <li><a href="/wiki/TAS2R20" title="TAS2R20">20</a></li> <li><a href="/wiki/TAS2R30" title="TAS2R30">30</a></li> <li><a href="/wiki/TAS2R31" title="TAS2R31">31</a></li> <li><a href="/wiki/TAS2R38" title="TAS2R38">38</a></li> <li><a href="/wiki/TAS2R39" title="TAS2R39">39</a></li> <li><a href="/wiki/TAS2R40" title="TAS2R40">40</a></li> <li><a href="/wiki/TAS2R41" title="TAS2R41">41</a></li> <li><a href="/wiki/TAS2R42" title="TAS2R42">42</a></li> <li><a href="/wiki/TAS2R43" title="TAS2R43">43</a></li> <li><a href="/wiki/TAS2R45" title="TAS2R45">45</a></li> <li><a href="/wiki/TAS2R46" title="TAS2R46">46</a></li> <li><a href="/wiki/TAS2R50" title="TAS2R50">50</a></li> <li><a href="/wiki/TAS2R60" title="TAS2R60">60</a></li></ul></li> <li><a href="/wiki/Vomeronasal_receptor" title="Vomeronasal receptor">Vomeronasal receptor</a> type 1</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><a href="/wiki/Orphan_receptor" title="Orphan receptor">Orphan</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>GPR</i> (<a href="/wiki/GPR1" title="GPR1">1</a></li> <li><a href="/wiki/GPR3" title="GPR3">3</a></li> <li><a href="/wiki/GPR4" title="GPR4">4</a></li> <li><a href="/wiki/GPR6" title="GPR6">6</a></li> <li><a href="/wiki/GPR12" title="GPR12">12</a></li> <li><a href="/wiki/GPR15" title="GPR15">15</a></li> <li><a href="/wiki/GPR17" title="GPR17">17</a></li> <li><a href="/wiki/GPR18" class="mw-redirect" title="GPR18">18</a></li> <li><a href="/wiki/GPR19" title="GPR19">19</a></li> <li><a href="/wiki/GPR20" title="GPR20">20</a></li> <li><a href="/wiki/GPR21" title="GPR21">21</a></li> <li><a href="/wiki/GPR22" title="GPR22">22</a></li> <li><a href="/wiki/LPAR4" title="LPAR4">23</a></li> <li><a href="/wiki/GPR25" title="GPR25">25</a></li> <li><a href="/wiki/GPR26" title="GPR26">26</a></li> <li><a href="/wiki/GPR27" title="GPR27">27</a></li> <li><a href="/wiki/GPR31" title="GPR31">31</a></li> <li><a href="/wiki/GPR32" title="GPR32">32</a></li> <li><a href="/wiki/GPR33" title="GPR33">33</a></li> <li><a href="/wiki/GPR34" title="GPR34">34</a></li> <li><a href="/wiki/GPR35" title="GPR35">35</a></li> <li><a href="/wiki/GPR37" title="GPR37">37</a></li> <li><a href="/wiki/GPR39" title="GPR39">39</a></li> <li><a href="/wiki/GPR42" title="GPR42">42</a></li> <li><a href="/wiki/GPR44" class="mw-redirect" title="GPR44">44</a></li> <li><a href="/wiki/GPR45" title="GPR45">45</a></li> <li><a href="/wiki/GPR50" title="GPR50">50</a></li> <li><a href="/wiki/GPR52" title="GPR52">52</a></li> <li><a href="/wiki/GPR55" title="GPR55">55</a></li> <li><a href="/wiki/GPR61" title="GPR61">61</a></li> <li><a href="/wiki/GPR62" title="GPR62">62</a></li> <li><a href="/wiki/GPR63" title="GPR63">63</a></li> <li><a href="/wiki/GPR65" title="GPR65">65</a></li> <li><a href="/wiki/GPR68" title="GPR68">68</a></li> <li><a href="/wiki/GPR75" title="GPR75">75</a></li> <li><a href="/wiki/GPR78" title="GPR78">78</a></li> <li><a href="/wiki/GPR81" class="mw-redirect" title="GPR81">81</a></li> <li><a href="/wiki/GPR82" title="GPR82">82</a></li> <li><a href="/wiki/GPR83" title="GPR83">83</a></li> <li><a href="/wiki/GPR84" title="GPR84">84</a></li> <li><a href="/wiki/GPR85" title="GPR85">85</a></li> <li><a href="/wiki/GPR87" title="GPR87">87</a></li> <li><a href="/wiki/GPR88" title="GPR88">88</a></li> <li><a href="/wiki/LPAR5" title="LPAR5">92</a></li> <li><a href="/wiki/GPR101" title="GPR101">101</a></li> <li><a href="/wiki/Pyroglutamylated_RFamide_peptide_receptor" title="Pyroglutamylated RFamide peptide receptor">103</a></li> <li><a href="/wiki/Niacin_receptor_1" class="mw-redirect" title="Niacin receptor 1">109A</a></li> <li><a href="/wiki/Niacin_receptor_2" class="mw-redirect" title="Niacin receptor 2">109B</a></li> <li><a href="/wiki/GPR119" title="GPR119">119</a></li> <li><a href="/wiki/GPR120" class="mw-redirect" title="GPR120">120</a></li> <li><a href="/wiki/GPR132" title="GPR132">132</a></li> <li><a href="/wiki/GPR135" title="GPR135">135</a></li> <li><a href="/wiki/GPR137B" title="GPR137B">137B</a></li> <li><a href="/wiki/GPR139" title="GPR139">139</a></li> <li><a href="/wiki/GPR141" title="GPR141">141</a></li> <li><a href="/wiki/GPR142" title="GPR142">142</a></li> <li><a href="/wiki/GPR146" title="GPR146">146</a></li> <li><a href="/wiki/GPR148" title="GPR148">148</a></li> <li><a href="/wiki/GPR149" title="GPR149">149</a></li> <li><a href="/wiki/GPR150" title="GPR150">150</a></li> <li><a href="/wiki/GPR151" title="GPR151">151</a></li> <li><a href="/wiki/GPR152" title="GPR152">152</a></li> <li><a href="/wiki/GPR153" title="GPR153">153</a></li> <li><a href="/wiki/GPR160" title="GPR160">160</a></li> <li><a href="/wiki/GPR161" title="GPR161">161</a></li> <li><a href="/wiki/GPR162" title="GPR162">162</a></li> <li><a href="/wiki/GPR171" title="GPR171">171</a></li> <li><a href="/wiki/GPR173" title="GPR173">173</a></li> <li><a href="/wiki/GPR174" title="GPR174">174</a></li> <li><a href="/wiki/GPR176" title="GPR176">176</a></li> <li><a href="/wiki/GPR177" class="mw-redirect" title="GPR177">177</a></li> <li><a href="/wiki/GPR182" title="GPR182">182</a></li> <li><a href="/wiki/GPR183" title="GPR183">183</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:7em;text-align:left;"><i>Other</i></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/GPR182" title="GPR182">Adrenomedullin</a></li> <li><a href="/wiki/Olfactory_receptor" title="Olfactory receptor">Olfactory</a></li> <li><a href="/wiki/Opsin" title="Opsin">Opsin</a> (<a href="/wiki/OPN3" title="OPN3">3</a></li> <li><a href="/wiki/Melanopsin" title="Melanopsin">4</a></li> <li><a href="/wiki/OPN5" title="OPN5">5</a></li> <li><a href="/wiki/OPN1LW" title="OPN1LW">1LW</a></li> <li><a href="/wiki/OPN1MW" title="OPN1MW">1MW</a></li> <li><a href="/wiki/OPN1SW" title="OPN1SW">1SW</a></li> <li><a href="/wiki/Retinal_G_protein_coupled_receptor" title="Retinal G protein coupled receptor">RGR</a></li> <li><a href="/wiki/RRH" title="RRH">RRH</a>)</li> <li><a href="/wiki/Protease-activated_receptor" title="Protease-activated receptor">Protease-activated</a> (<a href="/wiki/Coagulation_factor_II_receptor" class="mw-redirect" title="Coagulation factor II receptor">1</a></li> <li><a href="/wiki/Protease_activated_receptor_2" class="mw-redirect" title="Protease activated receptor 2">2</a></li> <li><a href="/wiki/F2RL2" title="F2RL2">3</a></li> <li><a href="/wiki/F2RL3" title="F2RL3">4</a>)</li> <li><a href="/wiki/Super_Conserved_Receptor_Expressed_in_Brain" title="Super Conserved Receptor Expressed in Brain">SREB</a> (<a href="/wiki/GPR27" title="GPR27">1</a></li> <li><a href="/wiki/GPR85" title="GPR85">2</a></li> <li><a href="/wiki/GPR173" title="GPR173">3</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Class_B:_Secretin-like" style="font-size:114%;margin:0 4em"><a href="/wiki/Secretin_receptor_family" title="Secretin receptor family">Class B</a>: <a href="/wiki/Secretin_receptor" title="Secretin receptor">Secretin</a>-like</div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;"><a href="/wiki/Adhesion_G_protein-coupled_receptor" title="Adhesion G protein-coupled receptor">Adhesion</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>ADGRB</i> <ul><li><a href="/wiki/Brain-specific_angiogenesis_inhibitor" title="Brain-specific angiogenesis inhibitor">Brain-specific angiogenesis inhibitor</a> <ul><li><a href="/wiki/Brain-specific_angiogenesis_inhibitor_1" title="Brain-specific angiogenesis inhibitor 1">1</a></li> <li><a href="/wiki/Brain-specific_angiogenesis_inhibitor_2" title="Brain-specific angiogenesis inhibitor 2">2</a></li> <li><a href="/wiki/Brain-specific_angiogenesis_inhibitor_3" title="Brain-specific angiogenesis inhibitor 3">3</a></li></ul></li></ul></li> <li><i>ADGRC</i> <ul><li><a href="/wiki/Flamingo_(protein)" title="Flamingo (protein)">Cadherin</a> <ul><li><a href="/wiki/CELSR1" title="CELSR1">1</a></li> <li><a href="/wiki/CELSR2" title="CELSR2">2</a></li> <li><a href="/wiki/CELSR3" title="CELSR3">3</a></li></ul></li></ul></li> <li><i>ADGRE</i> <ul><li><a href="/wiki/EGF_module-containing_mucin-like_hormone_receptor" title="EGF module-containing mucin-like hormone receptor">EMR</a> <ul><li><a href="/wiki/EMR1" title="EMR1">1</a></li> <li><a href="/wiki/EMR2" title="EMR2">2</a></li> <li><a href="/wiki/EMR3" title="EMR3">3</a></li></ul></li> <li><a href="/wiki/CD97" title="CD97">CD97</a></li></ul></li> <li><i>ADGRG</i> <ul><li><a href="/wiki/GPR56" title="GPR56">1</a></li> <li><a href="/wiki/GPR64" title="GPR64">2</a></li> <li><a href="/wiki/GPR97" title="GPR97">3</a></li> <li><a href="/wiki/GPR112" title="GPR112">4</a></li> <li><a href="/wiki/GPR114" title="GPR114">5</a></li> <li><a href="/wiki/GPR126" title="GPR126">6</a></li> <li><a href="/wiki/GPR128" title="GPR128">7</a></li></ul></li> <li><i>ADGRL</i> <ul><li><a href="/wiki/Latrophilin_receptor" class="mw-redirect" title="Latrophilin receptor">Latrophilin</a> <ul><li><a href="/wiki/Latrophilin_1" title="Latrophilin 1">1</a></li> <li><a href="/wiki/Latrophilin_2" title="Latrophilin 2">2</a></li> <li><a href="/wiki/Latrophilin_3" title="Latrophilin 3">3</a></li></ul></li> <li><a href="/wiki/ELTD1" class="mw-redirect" title="ELTD1">ELTD1</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;"><a href="/wiki/Orphan_receptor" title="Orphan receptor">Orphan</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>GPR</i> (<a href="/wiki/GPR56" title="GPR56">56</a></li> <li><a href="/wiki/GPR64" title="GPR64">64</a></li> <li><a href="/wiki/GPR97" title="GPR97">97</a></li> <li><a href="/wiki/GPR98" title="GPR98">98</a></li> <li><a href="/wiki/GPR110" title="GPR110">110</a></li> <li><a href="/wiki/GPR111" title="GPR111">111</a></li> <li><a href="/wiki/GPR112" title="GPR112">112</a></li> <li><a href="/wiki/GPR113" title="GPR113">113</a></li> <li><a href="/wiki/GPR114" title="GPR114">114</a></li> <li><a href="/wiki/GPR115" title="GPR115">115</a></li> <li><a href="/wiki/GPR116" title="GPR116">116</a></li> <li><a href="/wiki/GPR123" title="GPR123">123</a></li> <li><a href="/wiki/GPR124" title="GPR124">124</a></li> <li><a href="/wiki/GPR125" title="GPR125">125</a></li> <li><a href="/wiki/GPR126" title="GPR126">126</a></li> <li><a href="/wiki/GPR128" title="GPR128">128</a></li> <li><a href="/wiki/GPR133" title="GPR133">133</a></li> <li><a href="/wiki/GPR143" title="GPR143">143</a></li> <li><a href="/wiki/GPR144" title="GPR144">144</a></li> <li><a href="/wiki/GPR155" title="GPR155">155</a></li> <li><a href="/wiki/GPR157" title="GPR157">157</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;"><i>Other</i></th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calcitonin_receptor" title="Calcitonin receptor">Calcitonin</a></li> <li><a href="/wiki/CALCRL" title="CALCRL">CALCRL</a></li> <li><a href="/wiki/Corticotropin-releasing_hormone_receptor" title="Corticotropin-releasing hormone receptor">Corticotropin-releasing hormone</a> (<a href="/wiki/Corticotropin-releasing_hormone_receptor_1" title="Corticotropin-releasing hormone receptor 1">1</a></li> <li><a href="/wiki/Corticotropin-releasing_hormone_receptor_2" title="Corticotropin-releasing hormone receptor 2">2</a>)</li> <li><a href="/wiki/Glucagon_receptor_family" title="Glucagon receptor family">Glucagon</a> (<a href="/wiki/Glucagon_receptor" title="Glucagon receptor">GR</a></li> <li><a href="/wiki/Gastric_inhibitory_polypeptide_receptor" title="Gastric inhibitory polypeptide receptor">GIPR</a></li> <li><a href="/wiki/Glucagon-like_peptide-1_receptor" title="Glucagon-like peptide-1 receptor">GLP1R</a></li> <li><a href="/wiki/Glucagon-like_peptide-2_receptor" title="Glucagon-like peptide-2 receptor">GLP2R</a>)</li> <li><a href="/wiki/Growth-hormone-releasing_hormone_receptor" title="Growth-hormone-releasing hormone receptor">Growth-hormone-releasing hormone</a></li> <li><a href="/wiki/ADCYAP1R1" title="ADCYAP1R1">PACAPR1</a></li> <li><a href="/wiki/Orphan_receptor" title="Orphan receptor">GPR</a></li> <li><a href="/wiki/Methuselah-like_proteins" title="Methuselah-like proteins">Methuselah-like proteins</a></li> <li><a href="/wiki/Parathyroid_hormone_receptor" title="Parathyroid hormone receptor">Parathyroid hormone</a> (<a href="/wiki/Parathyroid_hormone_1_receptor" title="Parathyroid hormone 1 receptor">1</a></li> <li><a href="/wiki/Parathyroid_hormone_2_receptor" title="Parathyroid hormone 2 receptor">2</a>)</li> <li><a href="/wiki/Secretin_receptor" title="Secretin receptor">Secretin</a></li> <li><a href="/wiki/Vasoactive_intestinal_peptide_receptor" title="Vasoactive intestinal peptide receptor">Vasoactive intestinal peptide</a> (<a href="/wiki/VIPR1" title="VIPR1">1</a></li> <li><a href="/wiki/VIPR2" title="VIPR2">2</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Class_C:_Metabotropic_glutamate_/_pheromone" style="font-size:114%;margin:0 4em"><a href="/wiki/Class_C_GPCR" title="Class C GPCR">Class C</a>: <a href="/wiki/Metabotropic_receptor" title="Metabotropic receptor">Metabotropic</a> <a href="/wiki/Metabotropic_glutamate_receptor" title="Metabotropic glutamate receptor">glutamate</a> / <a href="/wiki/Pheromone" title="Pheromone">pheromone</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;"><a href="/wiki/Taste_receptor" title="Taste receptor">Taste</a>, sweet</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><i>TAS1R</i> <ul><li><a href="/wiki/TAS1R1" title="TAS1R1">1</a></li> <li><a href="/wiki/TAS1R2" title="TAS1R2">2</a></li> <li><a href="/wiki/TAS1R3" title="TAS1R3">3</a></li></ul></li> <li><a href="/wiki/Vomeronasal_receptor" title="Vomeronasal receptor">Vomeronasal receptor</a>, type 2</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;"><i>Other</i></th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calcium-sensing_receptor" title="Calcium-sensing receptor">Calcium-sensing receptor</a></li> <li><a href="/wiki/GABA_receptor" title="GABA receptor">GABA<sub>B</sub></a> (<a href="/wiki/GABBR1" title="GABBR1">1</a></li> <li><a href="/wiki/GABBR2" title="GABBR2">2</a>)</li> <li><a href="/wiki/Glutamate_receptor" title="Glutamate receptor">Glutamate receptor</a> (<a href="/wiki/Metabotropic_glutamate_receptor" title="Metabotropic glutamate receptor">Metabotropic glutamate</a> (<a href="/wiki/Metabotropic_glutamate_receptor_1" title="Metabotropic glutamate receptor 1">1</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_2" title="Metabotropic glutamate receptor 2">2</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_3" title="Metabotropic glutamate receptor 3">3</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_4" title="Metabotropic glutamate receptor 4">4</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_5" title="Metabotropic glutamate receptor 5">5</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_6" title="Metabotropic glutamate receptor 6">6</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_7" title="Metabotropic glutamate receptor 7">7</a></li> <li><a href="/wiki/Metabotropic_glutamate_receptor_8" title="Metabotropic glutamate receptor 8">8</a>))</li> <li><a href="/wiki/GPRC6A" title="GPRC6A">GPRC6A</a></li> <li><a href="/wiki/Orphan_receptor" title="Orphan receptor">GPR</a> (<a href="/wiki/GPR156" title="GPR156">156</a></li> <li><a href="/wiki/GPR158" title="GPR158">158</a></li> <li><a href="/wiki/GPR179" title="GPR179">179</a>)</li> <li><a href="/wiki/Retinoic_acid-inducible_orphan_G_protein-coupled_receptor" title="Retinoic acid-inducible orphan G protein-coupled receptor">RAIG</a> (<a href="/wiki/GPRC5A" title="GPRC5A">1</a></li> <li><a href="/wiki/GPRC5B" title="GPRC5B">2</a></li> <li><a href="/wiki/GPRC5C" title="GPRC5C">3</a></li> <li><a href="/wiki/GPRC5D" title="GPRC5D">4</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks mw-collapsible mw-collapsed navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Class_F:_Frizzled_&amp;_Smoothened" style="font-size:114%;margin:0 4em">Class F: <a href="/wiki/Frizzled" title="Frizzled">Frizzled</a> & <a href="/wiki/Smoothened" title="Smoothened">Smoothened</a></div></th></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;">Frizzled</th><td class="navbox-list-with-group navbox-list navbox-odd" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Frizzled" title="Frizzled">Frizzled</a> (<a href="/wiki/FZD1" class="mw-redirect" title="FZD1">1</a></li> <li><a href="/wiki/FZD2" class="mw-redirect" title="FZD2">2</a></li> <li><a href="/wiki/FZD3" class="mw-redirect" title="FZD3">3</a></li> <li><a href="/wiki/FZD4" class="mw-redirect" title="FZD4">4</a></li> <li><a href="/wiki/FZD5" class="mw-redirect" title="FZD5">5</a></li> <li><a href="/wiki/FZD6" class="mw-redirect" title="FZD6">6</a></li> <li><a href="/wiki/FZD7" class="mw-redirect" title="FZD7">7</a></li> <li><a href="/wiki/FZD8" class="mw-redirect" title="FZD8">8</a></li> <li><a href="/wiki/FZD9" class="mw-redirect" title="FZD9">9</a></li> <li><a href="/wiki/FZD10" class="mw-redirect" title="FZD10">10</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:10em;text-align:left;">Smoothened</th><td class="navbox-list-with-group navbox-list navbox-even" style="padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Smoothened" title="Smoothened">Smoothened</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <p class="mw-empty-elt"> </p>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" 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