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class="social-profile-avatar-container"><img class="profile-avatar u-positionAbsolute" alt="David Gurwitz" border="0" onerror="if (this.src != '//a.academia-assets.com/images/s200_no_pic.png') this.src = '//a.academia-assets.com/images/s200_no_pic.png';" width="200" height="200" src="https://0.academia-photos.com/42197411/33542483/29846027/s200_david.gurwitz.jpg" /></div><div class="title-container"><h1 class="ds2-5-heading-sans-serif-sm">David Gurwitz</h1><div class="affiliations-container fake-truncate js-profile-affiliations"><div><a class="u-tcGrayDarker" href="https://telaviv.academia.edu/">Tel Aviv University</a>, <a class="u-tcGrayDarker" href="https://telaviv.academia.edu/Departments/Human_Molecular_Genetics_and_Biochemistry/Documents">Human Molecular Genetics and Biochemistry</a>, <span class="u-tcGrayDarker">Faculty Member</span></div></div></div></div><div class="sidebar-cta-container"><button class="ds2-5-button hidden profile-cta-button grow js-profile-follow-button" data-broccoli-component="user-info.follow-button" data-click-track="profile-user-info-follow-button" data-follow-user-fname="David" data-follow-user-id="42197411" data-follow-user-source="profile_button" data-has-google="false"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">add</span>Follow</button><button class="ds2-5-button hidden profile-cta-button grow js-profile-unfollow-button" data-broccoli-component="user-info.unfollow-button" data-click-track="profile-user-info-unfollow-button" data-unfollow-user-id="42197411"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">done</span>Following</button></div></div><div class="user-stats-container"><a><div class="stat-container js-profile-followers"><p class="label">Followers</p><p class="data">50</p></div></a><a><div class="stat-container js-profile-followees" data-broccoli-component="user-info.followees-count" data-click-track="profile-expand-user-info-following"><p class="label">Following</p><p class="data">2</p></div></a><a><div class="stat-container js-profile-coauthors" data-broccoli-component="user-info.coauthors-count" data-click-track="profile-expand-user-info-coauthors"><p class="label">Co-author</p><p class="data">1</p></div></a><a href="https://telaviv.academia.edu/DavidGurwitz/Analytics"><div class="stat-container"><p class="label"><span class="js-profile-total-view-text">Public Views</span></p><p class="data"><span class="js-profile-view-count"></span></p></div></a></div><div class="ri-section"><div class="ri-section-header"><span>Interests</span></div><div class="ri-tags-container"><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="42197411" href="https://www.academia.edu/Documents/in/Insurgency_and_counterinsurgency"><div id="js-react-on-rails-context" style="display:none" 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data-dom-id="Pill-react-component-25c292cc-60de-48d9-8d84-95859fb9b9ff"></div> <div id="Pill-react-component-25c292cc-60de-48d9-8d84-95859fb9b9ff"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="42197411" href="https://www.academia.edu/Documents/in/Terrorism_and_Counterterrorism"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Terrorism and Counterterrorism"]}" data-trace="false" data-dom-id="Pill-react-component-4882ce2e-7954-45a5-a71a-7891d30677f8"></div> <div id="Pill-react-component-4882ce2e-7954-45a5-a71a-7891d30677f8"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="42197411" href="https://www.academia.edu/Documents/in/Public_Policy_Analysis"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Public Policy Analysis"]}" data-trace="false" data-dom-id="Pill-react-component-e1b0ec87-a0a6-4141-b804-f4b618ddb622"></div> <div id="Pill-react-component-e1b0ec87-a0a6-4141-b804-f4b618ddb622"></div> </a><a data-click-track="profile-user-info-expand-research-interests" data-has-card-for-ri-list="42197411" href="https://www.academia.edu/Documents/in/Futurology"><div class="js-react-on-rails-component" style="display:none" data-component-name="Pill" data-props="{"color":"gray","children":["Futurology"]}" data-trace="false" data-dom-id="Pill-react-component-90315315-c191-4bc3-8f3f-99a81ebdb355"></div> <div id="Pill-react-component-90315315-c191-4bc3-8f3f-99a81ebdb355"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by David Gurwitz</h3></div><div class="js-work-strip profile--work_container" data-work-id="21088844"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088844/Novel_5_HT_1A_receptor_agonists_F11440_MKC242_and_BAYx3702"><img alt="Research paper thumbnail of Novel 5-HT 1A-receptor agonists: F11440, MKC242 and BAYx3702" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088844/Novel_5_HT_1A_receptor_agonists_F11440_MKC242_and_BAYx3702">Novel 5-HT 1A-receptor agonists: F11440, MKC242 and BAYx3702</a></div><div class="wp-workCard_item"><span>Drug Discov Today</span><span>, 1999</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088844"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088844"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088844; 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id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088844]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088844,"title":"Novel 5-HT 1A-receptor agonists: F11440, MKC242 and BAYx3702","translated_title":"","metadata":{"publication_date":{"day":null,"month":null,"year":1999,"errors":{}},"publication_name":"Drug Discov 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088843"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088843/A_new_handle_on_Alzheimers_amyloid_toxicity"><img alt="Research paper thumbnail of A new handle on Alzheimer's amyloid toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088843/A_new_handle_on_Alzheimers_amyloid_toxicity">A new handle on Alzheimer's amyloid toxicity</a></div><div class="wp-workCard_item"><span>Mol Med Today</span><span>, 1998</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088843"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088843"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088843; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088843]").text(description); 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class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088842/Physical_activity_good_for_your_health_very_good_for_your_gene_expression_HotSpots">Physical activity: good for your health, very good for your gene expression: HotSpots</a></div><div class="wp-workCard_item"><span>Clin Genet</span><span>, 2001</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088842"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count 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class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088841/Cancer_therapy_A2B_adenosine_antagonists_for_busting_tumor_angiogenesis"><img alt="Research paper thumbnail of Cancer therapy: A2B adenosine antagonists for busting tumor angiogenesis?" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088841/Cancer_therapy_A2B_adenosine_antagonists_for_busting_tumor_angiogenesis">Cancer therapy: A2B adenosine antagonists for busting tumor angiogenesis?</a></div><div class="wp-workCard_item"><span>Molecular Medicine Today</span><span>, 2000</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span 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Lancet</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">... References. 1 Sourander L, Rajala T, Raiha I, Makinen J, Erkkola R, Helenius H. Cardiovascula...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">... References. 1 Sourander L, Rajala T, Raiha I, Makinen J, Erkkola R, Helenius H. Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088830"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate"><img alt="Research paper thumbnail of Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate">Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate</a></div><div class="wp-workCard_item"><span>Journal of Biological Chemistry</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis i...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088830"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088830"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088830; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088830]").text(description); $(".js-view-count[data-work-id=21088830]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088830; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088830']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088830, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088830]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088830,"title":"Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate","translated_title":"","metadata":{"abstract":"High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.","publication_date":{"day":null,"month":null,"year":2002,"errors":{}},"publication_name":"Journal of Biological Chemistry"},"translated_abstract":"High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.","internal_url":"https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate","translated_internal_url":"","created_at":"2016-01-28T21:43:29.293-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":42197411,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":42197411,"first_name":"David","middle_initials":null,"last_name":"Gurwitz","page_name":"DavidGurwitz","domain_name":"telaviv","created_at":"2016-01-27T04:47:41.138-08:00","display_name":"David Gurwitz","url":"https://telaviv.academia.edu/DavidGurwitz"},"attachments":[],"research_interests":[{"id":18520,"name":"Biological Chemistry","url":"https://www.academia.edu/Documents/in/Biological_Chemistry"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":64568,"name":"Humans","url":"https://www.academia.edu/Documents/in/Humans"},{"id":67484,"name":"Sequence alignment","url":"https://www.academia.edu/Documents/in/Sequence_alignment"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":99421,"name":"Spinal Cord","url":"https://www.academia.edu/Documents/in/Spinal_Cord"},{"id":121508,"name":"Jews","url":"https://www.academia.edu/Documents/in/Jews"},{"id":159958,"name":"Acetylcholine","url":"https://www.academia.edu/Documents/in/Acetylcholine"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons"},{"id":220742,"name":"Membrane transport proteins","url":"https://www.academia.edu/Documents/in/Membrane_transport_proteins"},{"id":260118,"name":"CHEMICAL SCIENCES","url":"https://www.academia.edu/Documents/in/CHEMICAL_SCIENCES"},{"id":372917,"name":"Protein Secondary Structure Prediction","url":"https://www.academia.edu/Documents/in/Protein_Secondary_Structure_Prediction"},{"id":386342,"name":"Sodium","url":"https://www.academia.edu/Documents/in/Sodium"},{"id":809881,"name":"Amino Acid Sequence","url":"https://www.academia.edu/Documents/in/Amino_Acid_Sequence"},{"id":990296,"name":"Choline","url":"https://www.academia.edu/Documents/in/Choline"},{"id":2260515,"name":"Chlorides","url":"https://www.academia.edu/Documents/in/Chlorides"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088829"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control"><img alt="Research paper thumbnail of The therapeutic potential of nicotine and nicotinic agonists for weight control" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control">The therapeutic potential of nicotine and nicotinic agonists for weight control</a></div><div class="wp-workCard_item"><span>Expert Opinion on Investigational Drugs</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smok...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer&amp;#39;s and Parkinson&amp;#39;s diseases, depression, attention deficit disorder, Tourette&amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088829"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088829"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088829; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088829]").text(description); $(".js-view-count[data-work-id=21088829]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088829; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088829']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088829, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088829]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088829,"title":"The therapeutic potential of nicotine and nicotinic agonists for weight control","translated_title":"","metadata":{"abstract":"Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer\u0026amp;#39;s and Parkinson\u0026amp;#39;s diseases, depression, attention deficit disorder, Tourette\u0026amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.","publication_date":{"day":null,"month":null,"year":1999,"errors":{}},"publication_name":"Expert Opinion on Investigational Drugs"},"translated_abstract":"Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer\u0026amp;#39;s and Parkinson\u0026amp;#39;s diseases, depression, attention deficit disorder, Tourette\u0026amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.","internal_url":"https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control","translated_internal_url":"","created_at":"2016-01-28T21:43:29.156-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":42197411,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":42197411,"first_name":"David","middle_initials":null,"last_name":"Gurwitz","page_name":"DavidGurwitz","domain_name":"telaviv","created_at":"2016-01-27T04:47:41.138-08:00","display_name":"David Gurwitz","url":"https://telaviv.academia.edu/DavidGurwitz"},"attachments":[],"research_interests":[],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088828"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088828/Editorial_CPPM_2013_Onward_Building_a_Socio_Technical_GPS_for_Global_Personalized_Medicine_A_Welcome_to_Editors_In_Chief_Adrian_LLerena_Spain_and_Ross_A_McKinnon_Australia_"><img alt="Research paper thumbnail of Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. McKinnon (Australia)" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088828/Editorial_CPPM_2013_Onward_Building_a_Socio_Technical_GPS_for_Global_Personalized_Medicine_A_Welcome_to_Editors_In_Chief_Adrian_LLerena_Spain_and_Ross_A_McKinnon_Australia_">Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. McKinnon (Australia)</a></div><div class="wp-workCard_item"><span>Current Pharmacogenomics and Personalized Medicine</span><span>, 2013</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088828"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088828"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088828; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088828]").text(description); $(".js-view-count[data-work-id=21088828]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088828; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088828']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088828, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088828]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088828,"title":"Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088795"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088795/Farm_Microbiome_and_Childhood_Asthma"><img alt="Research paper thumbnail of Farm Microbiome and Childhood Asthma" class="work-thumbnail" src="https://attachments.academia-assets.com/41709291/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088795/Farm_Microbiome_and_Childhood_Asthma">Farm Microbiome and Childhood Asthma</a></div><div class="wp-workCard_item"><span>New England Journal of Medicine</span><span>, 2011</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="b0223c9b30398bebae5a110055e0656c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":41709291,"asset_id":21088795,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/41709291/download_file?st=MTczMjY4MzkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088795"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088795"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088795; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088794"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088794/Recognition_of_the_muscarinic_receptor_by_its_endogenous_neurotransmitter_binding_of_3H_acetylcholine_and_its_modulation_by_transition_metal_ions_and_guanine_nucleotides"><img alt="Research paper thumbnail of Recognition of the muscarinic receptor by its endogenous neurotransmitter: binding of [3H]acetylcholine and its modulation by transition metal ions and guanine nucleotides" class="work-thumbnail" src="https://attachments.academia-assets.com/41709296/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088794/Recognition_of_the_muscarinic_receptor_by_its_endogenous_neurotransmitter_binding_of_3H_acetylcholine_and_its_modulation_by_transition_metal_ions_and_guanine_nucleotides">Recognition of the muscarinic receptor by its endogenous neurotransmitter: binding of [3H]acetylcholine and its modulation by transition metal ions and guanine nucleotides</a></div><div class="wp-workCard_item"><span>Proceedings of the National Academy of Sciences</span><span>, 1984</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="68d0934c2384c476e6fc4c66c01af59d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":41709296,"asset_id":21088794,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/41709296/download_file?st=MTczMjY4MzkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088794"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088794"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088794; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088793"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088793/Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors"><img alt="Research paper thumbnail of Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088793/Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors">Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors</a></div><div class="wp-workCard_item"><span>Biochemistry</span><span>, 1985</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. We propose that this differential response is due to the formation of ligand-receptor complexes that differ with respect to the microenvironment of the modified tyrosyl residue.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088793"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088793"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088793; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088793]").text(description); $(".js-view-count[data-work-id=21088793]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088793; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088793']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088793, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088793]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088793,"title":"Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors","translated_title":"","metadata":{"abstract":"Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. We propose that this differential response is due to the formation of ligand-receptor complexes that differ with respect to the microenvironment of the modified tyrosyl residue.","publication_date":{"day":null,"month":null,"year":1985,"errors":{}},"publication_name":"Biochemistry"},"translated_abstract":"Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088843"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088843/A_new_handle_on_Alzheimers_amyloid_toxicity"><img alt="Research paper thumbnail of A new handle on Alzheimer's amyloid toxicity" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088843/A_new_handle_on_Alzheimers_amyloid_toxicity">A new handle on Alzheimer's amyloid toxicity</a></div><div class="wp-workCard_item"><span>Mol Med Today</span><span>, 1998</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088843"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088843"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088843; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088832"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088832/Immunization_for_Alzheimers_disease_yet_closer_to_clinical_trials"><img alt="Research paper thumbnail of Immunization for Alzheimer's disease: yet closer to clinical trials" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088832/Immunization_for_Alzheimers_disease_yet_closer_to_clinical_trials">Immunization for Alzheimer's disease: yet closer to clinical trials</a></div><div class="wp-workCard_item"><span>Trends in Immunology</span><span>, 2001</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088832"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088832"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088832; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088831"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088831/Oestrogen_replacement_therapy_in_postmenopausal_women"><img alt="Research paper thumbnail of Oestrogen replacement therapy in postmenopausal women" class="work-thumbnail" src="https://attachments.academia-assets.com/41912058/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088831/Oestrogen_replacement_therapy_in_postmenopausal_women">Oestrogen replacement therapy in postmenopausal women</a></div><div class="wp-workCard_item"><span>The Lancet</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">... References. 1 Sourander L, Rajala T, Raiha I, Makinen J, Erkkola R, Helenius H. Cardiovascula...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">... References. 1 Sourander L, Rajala T, Raiha I, Makinen J, Erkkola R, Helenius H. Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy. Lancet 1998; 352: 1965-1969. ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="af7f16b4e65301a5bfbd711a71cc8e95" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":41912058,"asset_id":21088831,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/41912058/download_file?st=MTczMjY4MzkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088831"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088831"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088831; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088831]").text(description); $(".js-view-count[data-work-id=21088831]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088831; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088831']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088831, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "af7f16b4e65301a5bfbd711a71cc8e95" } } $('.js-work-strip[data-work-id=21088831]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088831,"title":"Oestrogen replacement therapy in postmenopausal women","translated_title":"","metadata":{"abstract":"... 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088830"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate"><img alt="Research paper thumbnail of Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate">Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate</a></div><div class="wp-workCard_item"><span>Journal of Biological Chemistry</span><span>, 2002</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis i...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088830"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088830"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088830; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088830]").text(description); $(".js-view-count[data-work-id=21088830]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088830; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088830']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088830, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088830]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088830,"title":"Single Nucleotide Polymorphism of the Human High Affinity Choline Transporter Alters Transport Rate","translated_title":"","metadata":{"abstract":"High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.","publication_date":{"day":null,"month":null,"year":2002,"errors":{}},"publication_name":"Journal of Biological Chemistry"},"translated_abstract":"High affinity choline uptake plays a critical role in the regulation of acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in molecular cloning of the high affinity choline transporter (CHT1), which is specifically expressed in cholinergic neurons. Here we demonstrate the presence of functionally relevant, nonsynonymous single nucleotide polymorphism in the human CHT1 gene by comprehensive sequence analysis of the exons and the intron/exon boundaries including the transcription start site. The deduced amino acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V) located within the third transmembrane domain of the protein. The allele frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for choline uptake rate compared with the wild type, whereas there was no alteration in the apparent affinities for choline, sodium, chloride, and the specific inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3 binding activity. The decreased choline uptake was not associated with the surface expression level of the protein as assessed by biotinylation assay. These results suggest an impaired substrate translocation in the I89V transporter. The Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding position and a single replacement from valine to isoleucine caused a decrease in the choline uptake rate by 40%, suggesting that this hydrophobic residue is generally critical in the choline transport rate in CHT1. This polymorphism in the allelic CHT1 gene may represent a predisposing factor for cholinergic dysfunction.","internal_url":"https://www.academia.edu/21088830/Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate","translated_internal_url":"","created_at":"2016-01-28T21:43:29.293-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":42197411,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Single_Nucleotide_Polymorphism_of_the_Human_High_Affinity_Choline_Transporter_Alters_Transport_Rate","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":42197411,"first_name":"David","middle_initials":null,"last_name":"Gurwitz","page_name":"DavidGurwitz","domain_name":"telaviv","created_at":"2016-01-27T04:47:41.138-08:00","display_name":"David Gurwitz","url":"https://telaviv.academia.edu/DavidGurwitz"},"attachments":[],"research_interests":[{"id":18520,"name":"Biological Chemistry","url":"https://www.academia.edu/Documents/in/Biological_Chemistry"},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences"},{"id":57808,"name":"Cell line","url":"https://www.academia.edu/Documents/in/Cell_line"},{"id":64568,"name":"Humans","url":"https://www.academia.edu/Documents/in/Humans"},{"id":67484,"name":"Sequence alignment","url":"https://www.academia.edu/Documents/in/Sequence_alignment"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":99421,"name":"Spinal Cord","url":"https://www.academia.edu/Documents/in/Spinal_Cord"},{"id":121508,"name":"Jews","url":"https://www.academia.edu/Documents/in/Jews"},{"id":159958,"name":"Acetylcholine","url":"https://www.academia.edu/Documents/in/Acetylcholine"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons"},{"id":220742,"name":"Membrane transport proteins","url":"https://www.academia.edu/Documents/in/Membrane_transport_proteins"},{"id":260118,"name":"CHEMICAL SCIENCES","url":"https://www.academia.edu/Documents/in/CHEMICAL_SCIENCES"},{"id":372917,"name":"Protein Secondary Structure Prediction","url":"https://www.academia.edu/Documents/in/Protein_Secondary_Structure_Prediction"},{"id":386342,"name":"Sodium","url":"https://www.academia.edu/Documents/in/Sodium"},{"id":809881,"name":"Amino Acid Sequence","url":"https://www.academia.edu/Documents/in/Amino_Acid_Sequence"},{"id":990296,"name":"Choline","url":"https://www.academia.edu/Documents/in/Choline"},{"id":2260515,"name":"Chlorides","url":"https://www.academia.edu/Documents/in/Chlorides"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088829"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control"><img alt="Research paper thumbnail of The therapeutic potential of nicotine and nicotinic agonists for weight control" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control">The therapeutic potential of nicotine and nicotinic agonists for weight control</a></div><div class="wp-workCard_item"><span>Expert Opinion on Investigational Drugs</span><span>, 1999</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smok...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer&amp;#39;s and Parkinson&amp;#39;s diseases, depression, attention deficit disorder, Tourette&amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088829"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088829"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088829; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088829]").text(description); $(".js-view-count[data-work-id=21088829]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088829; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088829']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088829, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088829]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088829,"title":"The therapeutic potential of nicotine and nicotinic agonists for weight control","translated_title":"","metadata":{"abstract":"Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer\u0026amp;#39;s and Parkinson\u0026amp;#39;s diseases, depression, attention deficit disorder, Tourette\u0026amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.","publication_date":{"day":null,"month":null,"year":1999,"errors":{}},"publication_name":"Expert Opinion on Investigational Drugs"},"translated_abstract":"Transdermal nicotine patches have been successfully introduced as a safe and powerful aid to smoking cessation; this has contributed to the rising interest in additional therapeutic applications for nicotine and synthetic nicotinic agonists. Nicotine and nicotinic agonists may have a therapeutic potential for a variety of disorders, including Alzheimer\u0026amp;#39;s and Parkinson\u0026amp;#39;s diseases, depression, attention deficit disorder, Tourette\u0026amp;#39;s syndrome and ulcerative colitis. These interests are partially fuelled by the urgent need of the tobacco industry to find new niches for nicotine in a world bound eventually to retire from cigarette smoking. At the same time, there is an increased interest in developing drugs for fighting obesity, a growing affliction of industrialised nations. This review presents data on the potential of nicotine, and in particular synthetic nicotinic agonists, for controlling body weight. Nicotinic agonists may become relatively safe, effective and inexpensive alternatives for several optional drugs currently being developed for treating human obesity, including beta-3-adrenergic agonists, leptin and its agonists, and neuropeptide Y antagonists.","internal_url":"https://www.academia.edu/21088829/The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control","translated_internal_url":"","created_at":"2016-01-28T21:43:29.156-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":42197411,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_therapeutic_potential_of_nicotine_and_nicotinic_agonists_for_weight_control","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":42197411,"first_name":"David","middle_initials":null,"last_name":"Gurwitz","page_name":"DavidGurwitz","domain_name":"telaviv","created_at":"2016-01-27T04:47:41.138-08:00","display_name":"David Gurwitz","url":"https://telaviv.academia.edu/DavidGurwitz"},"attachments":[],"research_interests":[],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088828"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088828/Editorial_CPPM_2013_Onward_Building_a_Socio_Technical_GPS_for_Global_Personalized_Medicine_A_Welcome_to_Editors_In_Chief_Adrian_LLerena_Spain_and_Ross_A_McKinnon_Australia_"><img alt="Research paper thumbnail of Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. McKinnon (Australia)" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088828/Editorial_CPPM_2013_Onward_Building_a_Socio_Technical_GPS_for_Global_Personalized_Medicine_A_Welcome_to_Editors_In_Chief_Adrian_LLerena_Spain_and_Ross_A_McKinnon_Australia_">Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. McKinnon (Australia)</a></div><div class="wp-workCard_item"><span>Current Pharmacogenomics and Personalized Medicine</span><span>, 2013</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088828"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088828"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088828; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088828]").text(description); $(".js-view-count[data-work-id=21088828]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088828; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088828']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088828, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088828]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088828,"title":"Editorial: CPPM 2013 Onward: Building a Socio-Technical GPS for Global Personalized Medicine – A Welcome to Editors-In-Chief Adrian LLerena (Spain) and Ross A. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="21088793"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/21088793/Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors"><img alt="Research paper thumbnail of Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/21088793/Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors">Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors</a></div><div class="wp-workCard_item"><span>Biochemistry</span><span>, 1985</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. We propose that this differential response is due to the formation of ligand-receptor complexes that differ with respect to the microenvironment of the modified tyrosyl residue.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="21088793"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="21088793"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 21088793; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=21088793]").text(description); $(".js-view-count[data-work-id=21088793]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 21088793; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='21088793']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 21088793, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=21088793]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":21088793,"title":"Increased agonist affinity is induced in tetranitromethane-modified muscarinic receptors","translated_title":"","metadata":{"abstract":"Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. We propose that this differential response is due to the formation of ligand-receptor complexes that differ with respect to the microenvironment of the modified tyrosyl residue.","publication_date":{"day":null,"month":null,"year":1985,"errors":{}},"publication_name":"Biochemistry"},"translated_abstract":"Tetranitromethane (TNM) modifies the muscarinic receptors from rat cerebral cortex. The modified receptor possesses an increased binding affinity (6-9-fold) toward several agonists such as acetylcholine, carbamoylcholine, arecoline, etc. The binding of antagonists (Bmax and Kd) is only slightly altered. The effects of TNM treatment can be prevented by atropine, thus indicating that TNM modifies residue(s) at the binding site. We carried out a series of successive chemical modifications which indicated that the modified residue(s) is (are) most probably a tyrosyl and not a cysteinyl residue. This conclusion gains support from the pH profile of agonist binding, which suggests the involvement of a residue with an apparent pK comparable to that of the phenolic hydroxyl of a nitrotyrosyl residue. The binding properties of the modified receptor, when compared to those of the native one, clearly indicate that the response to TNM modification with respect to the binding of agonists such as acetylcholine and carbamoylcholine is different from that when oxotremorine and its analogue are employed. This is interpreted as being the result of different binding modes exhibited by the various agonists. Nitration of the receptors can be prevented by the presence of an antagonist but not by an agonist. We propose that this differential response is due to the formation of ligand-receptor complexes that differ with respect to the microenvironment of the modified tyrosyl residue.","internal_url":"https://www.academia.edu/21088793/Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors","translated_internal_url":"","created_at":"2016-01-28T21:41:58.687-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":42197411,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Increased_agonist_affinity_is_induced_in_tetranitromethane_modified_muscarinic_receptors","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":42197411,"first_name":"David","middle_initials":null,"last_name":"Gurwitz","page_name":"DavidGurwitz","domain_name":"telaviv","created_at":"2016-01-27T04:47:41.138-08:00","display_name":"David Gurwitz","url":"https://telaviv.academia.edu/DavidGurwitz"},"attachments":[],"research_interests":[{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry"},{"id":4987,"name":"Kinetics","url":"https://www.academia.edu/Documents/in/Kinetics"},{"id":78467,"name":"Cerebral Cortex","url":"https://www.academia.edu/Documents/in/Cerebral_Cortex"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":111545,"name":"Male","url":"https://www.academia.edu/Documents/in/Male"},{"id":156347,"name":"Methane","url":"https://www.academia.edu/Documents/in/Methane"},{"id":159958,"name":"Acetylcholine","url":"https://www.academia.edu/Documents/in/Acetylcholine"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"}],"urls":[]}, dispatcherData: dispatcherData }); 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