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XXIII. The angiotensin II receptors | journal = Pharmacological Reviews | volume = 52 | issue = 3 | pages = 415–72 | date = September 2000 | pmid = 10977869 | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/52/3/415 }}</ref> They are important in the [[renin–angiotensin system]]: they are responsible for the [[signal transduction]] of the [[vasoconstriction|vasoconstricting]] stimulus of the main effector hormone, [[angiotensin|angiotensin II]].<ref name="pmid17346243">{{cite journal | vauthors = Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S | title = Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology | journal = Clinical Science | volume = 112 | issue = 8 | pages = 417–28 | date = April 2007 | pmid = 17346243 | doi = 10.1042/CS20060342 | s2cid = 27624282 }}</ref> == Structure == The [[angiotensin II receptor type 1|AT<sub>1</sub>]] and [[angiotensin II receptor type 2|AT<sub>2</sub>]] receptors share a sequence identity of ~30%, but have a similar affinity for angiotensin II, which is their main ligand. ==Members== ===Overview table=== {| class="wikitable" !Receptor !Mechanism<ref>Unless else specified in box, then ref is: [http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, Senselab] {{Webarchive|url=https://web.archive.org/web/20090228070451/http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, |date=2009-02-28 }}</ref> |- !AT<sub>1</sub> || *[[Gq alpha subunit|G<sub>q/11</sub>]] *[[Gi alpha subunit|G<sub>i/o</sub>]] |- !AT<sub>2</sub> || * [[Gi alpha subunit 2|G<sub>i2</sub>]] / [[Gi alpha subunit 3|<sub>3</sub>]] |- !AT<sub>3</sub> || |- !AT<sub>4</sub> || |- |} ===AT<sub>1</sub>===  {{Main|Angiotensin II receptor type 1}} The AT<sub>1</sub> receptor is the best elucidated angiotensin receptor. ====Location within the body==== The AT1 subtype is found in the heart, blood vessels, kidney, adrenal cortex, lung and [[circumventricular organs]] of brain, [[basal ganglia]], [[brainstem]]<ref>{{cite journal | vauthors = Allen AM, MacGregor DP, McKinley MJ, Mendelsohn FA | title = Angiotensin II receptors in the human brain | journal = Regulatory Peptides | volume = 79 | issue = 1 | pages = 1–7 | date = January 1999 | pmid = 9930578 | doi = 10.1016/S0167-0115(98)00138-4 | s2cid = 21317534 }}</ref> and mediates the vasoconstrictor effects. ====Mechanism==== The angiotensin receptor is activated by the [[vasoconstriction|vasoconstricting]] peptide [[angiotensin|angiotensin II]]. The activated receptor in turn couples to [[Gq alpha subunit|G<sub>q/11</sub>]] and [[Gi alpha subunit|G<sub>i/o</sub>]] and thus activates [[phospholipase|phospholipase C]] and increases the cytosolic Ca<sup>2+</sup> concentrations, which in turn triggers cellular responses such as stimulation of [[protein kinase C]]. Activated receptor also inhibits [[adenylate cyclase]] and activates various [[tyrosine kinase]]s.<ref name="pmid17346243" /> ====Effects==== Effects mediated by the AT<sub>1</sub> receptor include [[Vasoconstrictor|vasoconstriction]], [[aldosterone]] synthesis and secretion, increased [[vasopressin]] secretion, [[heart|cardiac]] [[Organ hypertrophy|hypertrophy]], augmentation of peripheral [[noradrenaline|noradrenergic activity]], [[blood vessel|vascular]] [[smooth muscle]] cells proliferation, decreased [[kidney|renal]] blood flow, renal [[renin]] inhibition, renal tubular [[sodium]] reuptake, modulation of central [[sympathetic nervous system]] activity, cardiac contractility, central [[osmoregulation|osmocontrol]] and [[extracellular matrix]] formation.<ref name="pmid6083400">{{cite journal | vauthors = Catt KJ, Mendelsohn FA, Millan MA, Aguilera G | title = The role of angiotensin II receptors in vascular regulation | journal = Journal of Cardiovascular Pharmacology | volume = 6 | issue = Suppl 4 | pages = S575-86 | year = 1984 | pmid = 6083400 | doi = 10.1097/00005344-198406004-00004 | doi-access = free }}</ref> ===AT<sub>2</sub>=== {{Main|Angiotensin II receptor type 2}} AT<sub>2</sub> receptors are more plentiful in the fetus and neonate. The AT<sub>2</sub> receptor remains enigmatic and controversial – is probably involved in vascular growth. Effects mediated by the AT<sub>2</sub> receptor are suggested to include inhibition of [[cell growth]], fetal tissue development, modulation of extracellular matrix, [[neuron]]al regeneration, [[apoptosis]], [[cellular differentiation]], and maybe [[vasodilation]] and [[left ventricular hypertrophy]].<ref name="pmid16286564">{{cite journal | vauthors = D'Amore A, Black MJ, Thomas WG | title = The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy | journal = Hypertension | volume = 46 | issue = 6 | pages = 1347–54 | date = December 2005 | pmid = 16286564 | doi = 10.1161/01.HYP.0000193504.51489.cf | s2cid = 10812400 | doi-access = }}</ref> In humans the AT2 subtype is found in molecular layer of the [[cerebellum]]. In the mouse is found in the adrenal gland, amygdaloid nuclei and, in small numbers, in the paraventricular nucleus of the hypothalamus and the locus coeruleus.<ref>{{cite journal | vauthors = Saavedra JM, Armando I | title = Angiotensin II AT2 Receptors Contribute to Regulate the Sympathoadrenal and Hormonal Reaction to Stress Stimuli | journal = Cellular and Molecular Neurobiology | volume = 38 | issue = 1 | pages = 85–108 | date = January 2018 | pmid = 28884431 | pmc = 6668356 | doi = 10.1007/s10571-017-0533-x }}</ref> ===AT<sub>3</sub> and AT<sub>4</sub>=== Other poorly characterized subtypes include the AT<sub>3</sub> and AT<sub>4</sub> receptors. The AT<sub>4</sub> receptor is activated by the angiotensin II metabolite [[angiotensin IV]], and may play a role in regulation of the CNS extracellular matrix, as well as modulation of [[oxytocin]] release.<ref name="pmid12591177">{{cite journal | vauthors = Albiston AL, Mustafa T, McDowall SG, Mendelsohn FA, Lee J, Chai SY | title = AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement | journal = Trends in Endocrinology and Metabolism | volume = 14 | issue = 2 | pages = 72–7 | date = March 2003 | pmid = 12591177 | doi = 10.1016/S1043-2760(02)00037-1 | s2cid = 6481079 }}</ref><ref name="pmid15549174">{{cite journal | vauthors = Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL | title = The angiotensin IV/AT4 receptor | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 21 | pages = 2728–37 | date = November 2004 | pmid = 15549174 | doi = 10.1007/s00018-004-4246-1 | s2cid = 22816307 }}</ref><ref name="pmid16343778">{{cite journal | vauthors = Davis CJ, Kramár EA, De A, Meighan PC, Simasko SM, Wright JW, Harding JW | title = AT4 receptor activation increases intracellular calcium influx and induces a non-N-methyl-D-aspartate dependent form of long-term potentiation | journal = Neuroscience | volume = 137 | issue = 4 | pages = 1369–79 | year = 2006 | pmid = 16343778 | doi = 10.1016/j.neuroscience.2005.10.051 | s2cid = 8280334 }}</ref><ref name="pmid19071192">{{cite journal | vauthors = Vanderheyden PM | title = From angiotensin IV binding site to AT4 receptor | journal = Molecular and Cellular Endocrinology | volume = 302 | issue = 2 | pages = 159–66 | date = April 2009 | pmid = 19071192 | doi = 10.1016/j.mce.2008.11.015 | s2cid = 140205109 }}</ref><ref name="pmid20224888">{{cite journal | vauthors = Beyer CE, Dwyer JM, Platt BJ, Neal S, Luo B, Ling HP, Lin Q, Mark RJ, Rosenzweig-Lipson S, Schechter LE | display-authors = 6 | title = Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation | journal = Psychopharmacology | volume = 209 | issue = 4 | pages = 303–11 | date = May 2010 | pmid = 20224888 | doi = 10.1007/s00213-010-1791-1 | s2cid = 7892428 | author-link2 = John Dwyer (medicine) }}</ref><ref>{{cite thesis | degree = Ph.D. | title = Design and Synthesis of Angiotensin IV Peptidomimetics Targeting the Insulin-Regulated Aminopeptidase (IRAP) | url = http://kth.diva-portal.org/smash/get/diva2:309698/FULLTEXT01 | author = Andersson H | year = 2010 | publisher = Uppsala Universitet | access-date = 2012-01-08 }}</ref><ref name="pmid21777652">{{cite journal | vauthors = Wright JW, Harding JW | title = Brain renin-angiotensin--a new look at an old system | journal = Progress in Neurobiology | volume = 95 | issue = 1 | pages = 49–67 | date = September 2011 | pmid = 21777652 | doi = 10.1016/j.pneurobio.2011.07.001 | s2cid = 25955824 }}</ref><ref name="pmid21719467">{{cite journal | vauthors = Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW | title = Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 339 | issue = 1 | pages = 35–44 | date = October 2011 | pmid = 21719467 | pmc = 3186286 | doi = 10.1124/jpet.111.182220 }}</ref> == See also == * [[Angiotensin II receptor antagonist]] == References == {{Reflist|colwidth=35em}} == External links == * {{MeshName|Receptors,+Angiotensin}} {{G protein-coupled receptors}} {{Neuropeptide receptors}} {{Angiotensin receptor modulators}} {{DEFAULTSORT:Angiotensin receptor}} [[Category:G protein-coupled receptors]] </textarea><div class="templatesUsed"><div class="mw-templatesUsedExplanation"><p><span id="templatesused">Pages transcluded onto the current version of this page<span class="posteditwindowhelplinks"> (<a 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