5-HT receptor 736392 223903488 2008-07-06T12:44:28Z It Is Me Here 2552569 Replaced PNG with SVG In the field of [[neurochemistry]], '''5-HT receptors''' are [[receptor (biochemistry)|receptors]] for the [[neurotransmitter]] and [[Periphery|peripheral]] signal mediator [[serotonin]], also known as 5-hydroxytryptamine or 5-HT.<ref name="pmid7938165">{{cite journal | author = Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP | title = International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin) | journal = Pharmacol. Rev. | volume = 46 | issue = 2 | pages = 157–203 | year = 1994 | pmid = 7938165 | doi = | issn = | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/46/2/157}}</ref> 5-HT receptors are located on the cell membrane of [[Neuron|nerve cells]] and other cell types including smooth muscle in animals, and mediate the effects of serotonin as the [[endogenous]] [[ligand]] and of a broad range of pharmaceutical and [[Psychedelics, dissociatives and deliriants|hallucinogenic drugs]]. 5-HT receptors affect the release and activity of other neurotransmitters such as [[glutamate]], [[dopamine]] and [[GABA]]. 5-HT<sub>2A</sub> receptors increase the activity of glutamate in many areas of the brain, while some other serotonin receptors have the effect of suppressing glutamate. Increased stimulation of 5-HT<sub>2A</sub> receptors seem to oppose the therapeutic actions of increased stimulation of other serotonin receptors in [[anti-depressant]] and [[anxiolytic]] treatments.<ref name="pmid12589395">{{cite journal | author = Marek GJ, Carpenter LL, McDougle CJ, Price LH | title = Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders | journal = Neuropsychopharmacology | volume = 28 | issue = 2 | pages = 402–12 | year = 2003 | pmid = 12589395 | doi = 10.1038/sj.npp.1300057 }}</ref> [[Image:Serotonin (5-HT).svg |thumb|[[Serotonin]]]] ==Classification== With the exception of the [[5-HT3 receptor|5-HT<sub>3</sub> receptor]], a [[ligand gated ion channel]], all other 5-HT receptors are [[G-protein-coupled receptor|G protein coupled seven transmembrane]] (or ''heptahelical'') receptors that activate an [[intracellular]] [[second messenger]] cascade. ===Families=== {| class="wikitable" | '''Family''' || '''Type''' || '''Mechanism''' |- | '''[[5-HT1|5-HT<sub>1</sub>]]''' || [[Gi alpha subunit|G<sub>i</sub>/G<sub>o</sub>]] coupled || decreasing cellular levels of [[cyclic adenosine monophosphate|cAMP]] |- | '''[[5-HT2|5-HT<sub>2</sub>]]''' || [[Gq protein|G<sub>q</sub>/G<sub>11</sub>]] coupled || increasing cellular levels of [[inositol trisphosphate]] (IP<sub>3</sub>) and [[diglyceride|diacylglycerol]] (DAG) |- | '''[[5-HT3|5-HT<sub>3</sub>]]''' || ligand-gated [[sodium|Na<sup>+</sup>]] and [[potassium|K<sup>+</sup>]] [[ion channels|cation channel]] || [[depolarization|depolarizing]] [[plasma membrane]] |- | '''[[5-HT4|5-HT<sub>4</sub>]]''' || [[G(s)alpha|G<sub>s</sub>]] coupled || increasing cellular levels of cAMP |- | '''[[5-HT5A|5-HT<sub>5A</sub>]]''' || [[G protein]] coupled; the primary coupling appears to be through Gi/o || inhibiting [[adenylate cyclase]] activity.<ref name="Nelson">{{cite journal | author = Nelson DL | title = 5-HT<sub>5</sub> receptors | journal = Current drug targets. CNS and neurological disorders | volume = 3 | issue = 1 | pages = 53–8 | year = 2004 | pmid = 14965244 | doi = | issn = | url = http://www.ingentaconnect.com/content/ben/cdtcnsnd/2004/00000003/00000001/art00006}}</ref> |- | '''[[5-HT6|5-HT<sub>6</sub>]]''' || [[G(s)alpha|G<sub>s</sub>]] coupled || increasing cellular levels of cAMP |- | '''[[5-HT7|5-HT<sub>7</sub>]]''' || [[G(s)alpha|G<sub>s</sub>]] coupled || increasing cellular levels of cAMP |} ===Specific proteins/genes=== Within these general classes of 5-HT receptors, a number of specific types have been characterized: {| class="wikitable" |+ Summary of characterized 5-HT receptors, with selected high affinity agonist and antagonist [[ligand (biochemistry)|ligands]] |- ! Receptor ! Gene ! Actions ! [[Agonist]]s ! [[Receptor antagonist|Antagonist]]s |- ! [[5-HT1A receptor|5-HT<sub>1A</sub>]] | {{Gene|HTR1A}} | *[[Central nervous system|CNS]]: neuronal inhibition, behavioural effects (sleep, feeding, [[thermoregulation]], aggression, anxiety) | *[[buspirone]] *[[psilocin]] *[[LSD]] *[[8-OH-DPAT]] | *[[spiperone]] *[[methiothepin]] *[[ergotamine]] *[[yohimbine]] |- ! [[5-HT1B receptor|5-HT<sub>1B</sub>]] | {{Gene|HTR1B}} | *CNS: [[presynaptic inhibition]], behavioural effects *vascular: pulmonary [[vasoconstriction]] | *ergotamine *[[sumatriptan]] | *methiothepin *[[yohimbine]] *[[metergoline]] *[[Risperidone]] |- ! [[5-HT1D receptor|5-HT<sub>1D</sub>]] | {{Gene|HTR1D}} | *CNS: locomotion, anxiety; *vascular: cerebral [[vasoconstriction]] | *5-(Nonyloxy)tryptamine,<ref name="Glennon_et_al_94">{{cite journal | author = Glennon RA, Hong SS, Dukat M, Teitler M, Davis K | title = 5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT<sub>1D</sub> beta serotonin receptor agonist | journal = J. Med. Chem. | volume = 37 | issue = 18 | pages = 2828–30 | year = 1994 | pmid = 8071931 | doi = 10.1021/jm00044a001 }}</ref> *sumatriptan | *methiothepin *yohimbine *metergoline *ergotamine |- ! [[5-HT1E|5-HT<sub>1E</sub>]] | {{Gene|HTR1E}} | | | |- ! [[5-HT1F|5-HT<sub>1F</sub>]] | {{Gene|HTR1F}} | | |- ! [[5-HT2A receptor|5-HT<sub>2A</sub>]] | {{Gene|HTR2A}} | *CNS: neuronal excitation, behavioural effects, learning, anxiety *smooth muscle: contraction, [[vasoconstriction]] / [[vasodilatation]] *platelets: aggregation | *[[α-methyl-5-HT]] *[[LSD]] *[[psilocin]] *[[2,5-Dimethoxy-4-iodoamphetamine|DOI]] | *[[Nefazodone]] *[[trazodone]] *[[mirtazapine]] *[[ketanserin]] *[[cyproheptadine]] *[[pizotifen]] *[[atypical antipsychotics]] |- ! [[5-HT2B receptor|5-HT<sub>2B</sub>]] | {{Gene|HTR2B}} | *stomach: contraction | *α-methyl-5-HT *[[LSD]] *[[2,5-Dimethoxy-4-iodoamphetamine|DOI]] *[[Fenfluramine]] | *[[yohimbine]] |- ! [[5-HT2C receptor|5-HT<sub>2C</sub>]] | {{Gene|HTR2C}} | *CNS: anxiety, [[choroid plexus]]: [[cerebrospinal fluid]] (CSF) secretion | *α-methyl-5-HT *[[agomelatine]] *[[LSD]] *[[psilocin]] *[[2,5-Dimethoxy-4-iodoamphetamine|DOI]] | *[[mesulergine]] *[[agomelatine]] *[[fluoxetine]] *[[methysergide]]<ref name=Rang187> {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 187 </ref> |- ! [[5-HT3 receptor|5-HT<sub>3</sub>]] | {{Gene|HTR3A}}, {{Gene|HTR3B}} | *CNS, [[peripheral nervous system|PNS]]: neuronal excitation, anxiety, [[emesis]] | *2-methyl-5-HT | *[[metoclopramide]] (high doses) *[[renzapride]] *[[ondansetron]] *[[alosetron]] *[[mirtazapine]] *[[memantine]] |- ! [[5-HT4 receptor|5-HT<sub>4</sub>]] | {{Gene|HTR4}} | *[[gastrointestinal tract|GIT]]: gastrointestinal motility *CNS: neuronal excitation, learning, memory | *[[5-methoxytryptamine]] *[[metoclopramide]] *[[cisapride]] *[[renzapride]] *[[tegaserod]] *[[RS 67333]] | *GR113808 *Piboserod |- ![[5-HT5A receptor|5-HT<sub>5A</sub>]] | {{Gene|HTR5A}} | *CNS ([[Cerebral cortex|cortex]], [[hippocampus]], [[cerebellum]]): unknown | *[[5-carboxytryptamine]] *<br>LSD<ref name="Nelson"/> | unknown |- ! [[5-HT6 receptor|5-HT<sub>6</sub>]] | {{Gene|HTR6}} | *CNS: unknown | *LSD | [[SB271046]]<ref name="titleTarget Schizophrenia - Possible future developments">{{cite web | url = http://www.abpi.org.uk/publications/publication_details/targetSchizophrenia-2003/section5.asp | title = Target Schizophrenia - Possible future developments | accessdate = 2008-04-11 | author = | authorlink = | coauthors = | date = | format = | work = | publisher = The Association of the British Pharmaceutical Industry | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> |- ! [[5-HT7 receptor|5-HT<sub>7</sub>]] | {{Gene|HTR7}} | *CNS, GIT, blood vessels: unknown | *5-carboxytryptamine *LSD | *methiothepin *[[risperidone]] |} Note that there is no 5-HT<sub>1C</sub> receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT<sub>2</sub> family of receptors and was redesignated as the 5-HT<sub>2C</sub> receptor. ==Therapeutic modulation== Various [[medication|drugs]] are used to modulate the 5-HT system including some [[antidepressant]]s, [[anxiolytic]]s, [[antiemetic]]s, [[antipsychotics]] and [[triptan|anti-migraine agents]]. ==References== {{Reflist|2}} === Other === * {{Cite journal | author = [[David E. Nichols]] and [[Charles D. Nichols]] | title = Serotonin Receptors | journal = [[Chem. Rev.]] | volume = 108 | issue = 5 | pages = 1614&ndash;1641 | year = 2008 | pmid = 18476671 | doi = 10.1021/cr078224o | url = http://pubs.acs.org/cgi-bin/article.cgi/chreay/2008/108/i05/html/cr078224o.html }} ==External links== * {{MeshName|Serotonin+Receptors}} * {{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1288 | title = 5-Hydroxytryptamine Receptors | accessdate = 2008-04-11 | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Receptor Database | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }} * {{cite web | url = http://www.acnp.org/g4/GN401000039/Ch039.html | title = Serotonin Receptor Subtypes and Ligands | accessdate = 2008-04-11 | author = Glennon RA, Dukat M, Westkaemper RB | authorlink = | coauthors = | date = 2000-01-01 | format = | work = | publisher = American College of Neurophyscopharmacology | pages = | language = | archiveurl = | archivedate = | quote = }} * {{cite web | url = http://cogprints.org/4095/ | title = Activation of G protein-coupled receptors entails cysteine modulation of agonist binding | author = Rubenstein, LA, Lanzara RG | authorlink = | coauthors = | accessdate = 2008-04-11 | date = 2005-02-16 | format = | work = | publisher = Cogprints | pages = | language = | archiveurl = | archivedate = | quote = }} * {{cite book | author = Frazer A, Hensler JG | editor = Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors | title = Basic Neurochemistry: Molecular, Cellular, and Medical Aspects | publisher = Lippincott-Raven | location = Philadelphia | year = 1999 | pages = | isbn = 0-397-51820-X | oclc = | doi = | pages = pages 263-292 | chapter= Chapter 13: Serotonin Receptors | chapterurl = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=bnchm.section.963 | accessdate = 2008-04-11 }} * {{cite journal |author=Wesołowska A |title=In the search for selective ligands of 5-HT<sub>5</sub>, 5-HT<sub>6</sub> and 5-HT<sub>7</sub> serotonin receptors |journal=Polish Journal of Pharmacology |volume=54 |issue=4 |pages=327–41 |year=2002 |pmid=12523486 |url=http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf}} {{G protein-coupled receptors}} {{Ligand-gated ion channels}} [[Category:G protein coupled receptors]] [[Category:Ionotropic receptors]] [[de:5-HT-Rezeptor]] [[ja:セロトニン受容体]]