Editing Serotonin (section)

====Receptors====
{{Main|Serotonin receptor}}

The [[serotonin receptor]]s are located on the [[cell membrane]] of [[Neuron|nerve cells]] and other cell types in animals, and mediate the effects of serotonin as the [[endogenous]] [[ligand]] and of a broad range of pharmaceutical and [[Psychedelics|psychedelic drug]]s. There are currently 14{{nbsp}}known serotonin receptors, including the serotonin [[5-HT1 receptor|5-HT<sub>1</sub>]] (<sub>[[5-HT1A receptor|1A]]</sub>, <sub>[[5-HT1B receptor|1B]]</sub>, <sub>[[5-HT1D receptor|1D]]</sub>, <sub>[[5-HT1E receptor|1E]]</sub>, <sub>[[5-HT1F receptor|1F]]</sub>), [[5-HT2 receptor|5-HT<sub>2</sub>]] (<sub>[[5-HT2A receptor|2A]]</sub>, <sub>[[5-HT2B receptor|2B]]</sub>, <sub>[[5-HT2C receptor|2C]]</sub>), [[5-HT3 receptor|5-HT<sub>3</sub>]], [[5-HT4 receptor|5-HT<sub>4</sub>]], [[5-HT5 receptor|5-HT<sub>5</sub>]] (<sub>[[5-HT5A receptor|5A]]</sub>, <sub>[[5-HT5B receptor|5B]]</sub>), [[5-HT6 receptor|5-HT<sub>6</sub>]], and [[5-HT7 receptor|5-HT<sub>7</sub> receptor]]s. Except for the serotonin [[5-HT3|5-HT<sub>3</sub> receptor]], a ligand-gated [[ion channel]], all other 5-HT receptors are [[G-protein-coupled receptors]] (also called seven-transmembrane, or heptahelical receptors) that activate an [[intracellular]] [[second messenger]] cascade.<ref name="pmid18571247">{{cite journal | vauthors = Hannon J, Hoyer D | title = Molecular biology of 5-HT receptors | journal = Behavioural Brain Research | volume = 195 | issue = 1 | pages = 198–213 | date = December 2008 | pmid = 18571247 | doi = 10.1016/j.bbr.2008.03.020 | s2cid = 46043982 }}</ref> The 5-HT<sub>5B</sub> receptor is present in rodents but not in humans.

In addition to the serotonin receptors, serotonin is an [[agonist]] of the [[trace amine-associated receptor 1]] (TAAR1) in some species.<ref name="GainetdinovHoenerBerry2018">{{cite journal | vauthors = Gainetdinov RR, Hoener MC, Berry MD | title = Trace Amines and Their Receptors | journal = Pharmacol Rev | volume = 70 | issue = 3 | pages = 549–620 | date = July 2018 | pmid = 29941461 | doi = 10.1124/pr.117.015305 | url = | doi-access = free }}</ref><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA| archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-date = 9 May 2025 }}</ref> It is a weak TAAR1 [[partial agonist]] in rats, but is inactive at the TAAR1 in mice and humans.<ref name="GainetdinovHoenerBerry2018" /><ref name="SimmlerBuchyChaboz2016" />

The [[cryo-EM]] [[protein–ligand complex|structure]]s of the serotonin 5-HT<sub>2A</sub> receptor with serotonin, as well as with various [[serotonergic psychedelic]]s, have been solved and published by [[Bryan L. Roth]] and colleagues.<ref name="GumpperJainKim2025">{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | pages = 2734 | date = March 2025 | pmid = 40108183 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | bibcode = 2025NatCo..16.2734G }}</ref><ref name="GumpperDiBertoJain2022">{{cite conference | vauthors = Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL | title = Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias | conference = University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat September 16th, 2022 – William and Ida Friday Center | date = September 2022 | url = https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37}}</ref>