{"id":6377,"date":"2023-02-17T06:57:16","date_gmt":"2023-02-17T06:57:16","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-an-electrophysiological-characterization-of-naturally-occurring-tobacco-alkaloids-and-their-action-on-human-%ce%b14%ce%b22-and-%ce%b17-nicotinic-acetylcholine-receptors\/"},"modified":"2023-02-17T06:57:17","modified_gmt":"2023-02-17T06:57:17","slug":"2020-an-electrophysiological-characterization-of-naturally-occurring-tobacco-alkaloids-and-their-action-on-human-%ce%b14%ce%b22-and-%ce%b17-nicotinic-acetylcholine-receptors","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2020-an-electrophysiological-characterization-of-naturally-occurring-tobacco-alkaloids-and-their-action-on-human-%ce%b14%ce%b22-and-%ce%b17-nicotinic-acetylcholine-receptors\/","title":{"rendered":"2020 &#8211; An electrophysiological characterization of naturally occurring tobacco alkaloids and their action on human \u03b14\u03b22 and \u03b17 nicotinic acetylcholine receptors"},"content":{"rendered":"<p>Nicotinic acetylcholine receptor (nAChR) subtype-selective pharmacological profiles of tobacco alkaloids are essential for understanding the physiological effects of tobacco products. In this study, automated electrophysiology was used to functionally characterize the effects of distinct groups of tobacco alkaloids on human \u03b14\u03b22 and \u03b17 nAChRs. We found that, in tobacco alkaloids, pyridine as a hydrogen bond acceptor and a basic nitrogen atom at a distance of 4\u20137\u202f\u00c5 are pharmacophoric elements necessary for molecular recognition by \u03b14\u03b22 and \u03b17 nAChRs with various degrees of selectivity, potency, and efficacy. While four alkaloids\u2014nicotine, nornicotine, anabasine and R-anatabine\u2014potently activated \u03b14\u03b22, they were also weak agonists of \u03b17 nAChRs. Nicotine was the most potent agonist of \u03b14\u03b22, while anabasine elicited the highest activation of \u03b17. None of the tobacco alkaloids enhanced nAChR activity elicited by the endogenous ligand acetylcholine; therefore, none was considered to be a positive allosteric modulator (PAM) of either \u03b14\u03b22 or \u03b17 nAChRs. In contrast, we identified tobacco alkaloids, such as the tryptophan metabolite 6-hydroxykynurenic acid, that decreased the activity of both \u03b14\u03b22 and \u03b17 nAChRs. Our study identified a class of alkaloids with positive and negative effects against human \u03b14\u03b22 and \u03b17 nAChRs. It also revealed human \u03b14\u03b22 to be the principal receptor for sensing the most abundant alkaloids in tobacco leaves.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[337],"target_families":[360],"targets":[189,194],"resource_keyword":[],"class_list":["post-6377","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","target_categories-ligand-gated-ion-channels","target_families-nicotinic-acetylcholine-receptors","targets-achr-7","targets-achr-4-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6377","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6377"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6377"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6377"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6377"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6377"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6377"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6377"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6377"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6377"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}