5-HT receptor
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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 = 1614–1641
| 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]]