5-HT4 receptor

This gene is a member of the family of human serotonin receptors, which are G protein-coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described, but the full-length nature of some transcript variants has not been determined.{{cite web| title = Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3360}}

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS).{{cite journal | vauthors = Hegde SS, Eglen RM | title = Peripheral 5-HT4 receptors | journal = FASEB Journal | volume = 10 | issue = 12 | pages = 1398–407 | date = October 1996 | pmid = 8903510 | doi = 10.1096/fasebj.10.12.8903510 | doi-access = free | s2cid = 21596751 }}

In the CNS the receptor appears in the putamen, caudate nucleus, nucleus accumbens, globus pallidus, and substantia nigra, and to a lesser extent in the neocortex, raphe, pontine nuclei, and some areas of the thalamus.

It has not been found in the cerebellum.{{cite journal | vauthors = Varnäs K, Halldin C, Pike VW, Hall H | title = Distribution of 5-HT4 receptors in the postmortem human brain--an autoradiographic study using [125I]SB 207710 | journal = European Neuropsychopharmacology | volume = 13 | issue = 4 | pages = 228–34 | date = August 2003 | pmid = 12888181 | doi = 10.1016/S0924-977X(03)00009-9 | s2cid = 27945284 }}

Internalization is isoform-specific.{{cite journal | vauthors = Mnie-Filali O, Amraei MG, Benmbarek S, Archer-Lahlou E, Peñas-Cazorla R, Vilaró MT, Boye SM, Piñeyro G | title = Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: effects of 5-HT and RS67333 on isoforms A and B | journal = Cellular Signalling | volume = 22 | issue = 3 | pages = 501–9 | date = March 2010 | pmid = 19922792 | doi = 10.1016/j.cellsig.2009.11.004 }}

Several drugs that act as 5-HT₄ selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs that act as 5-HT₄ agonists are also active as 5-HT₃ antagonists, such as mosapride, metoclopramide, renzapride, and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.{{cite journal | vauthors = Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L | title = Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors | journal = Molecular Pharmacology | volume = 75 | issue = 4 | pages = 982–90 | date = April 2009 | pmid = 19168624 | doi = 10.1124/mol.108.053686 | s2cid = 17957338 | url = https://hal.archives-ouvertes.fr/hal-02483472/file/2009%20MolPharm%20Pellissier.pdf }} Amongst these agonists prucalopride has >150-fold higher affinity for 5-HT4 receptors than for other receptors.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT₄ in positron emission tomography pig{{cite journal | vauthors = Kornum BR, Lind NM, Gillings N, Marner L, Andersen F, Knudsen GM | title = Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Göttingen minipig | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 29 | issue = 1 | pages = 186–96 | date = January 2009 | pmid = 18797470 | doi = 10.1038/jcbfm.2008.110 | doi-access = free }}

and human{{cite journal | vauthors = Marner L, Gillings N, Comley RA, Baaré WF, Rabiner EA, Wilson AA, Houle S, Hasselbalch SG, Svarer C, Gunn RN, Laruelle M, Knudsen GM | title = Kinetic modeling of 11C-SB207145 binding to 5-HT4 receptors in the human brain in vivo | journal = Journal of Nuclear Medicine | volume = 50 | issue = 6 | pages = 900–8 | date = June 2009 | pmid = 19470850 | doi = 10.2967/jnumed.108.058552 | doi-access = free }}

studies.

• Tropisetron{{cite journal | vauthors = Costall B, Naylor RJ | title = The pharmacology of the 5-HT4 receptor | journal = International Clinical Psychopharmacology | volume = 8 Suppl 2 | issue = Suppl 2 | pages = 11–18 | date = November 1993 | pmid = 8201242 | doi = 10.1097/00004850-199311002-00002 | s2cid = 36692776 }}{{snd}} partial agonist
• BIMU-8
• Cisapride
• CJ-033,466{{snd}} partial agonist
• Felcisetrag
• ML-10302{{cite journal | vauthors = Godínez-Chaparro B, Barragán-Iglesias P, Castañeda-Corral G, Rocha-González HI, Granados-Soto V | title = Role of peripheral 5-HT(4), 5-HT(6), and 5-HT(7) receptors in development and maintenance of secondary mechanical allodynia and hyperalgesia | journal = Pain | volume = 152 | issue = 3 | pages = 687–97 | date = March 2011 | pmid = 21239110 | doi = 10.1016/j.pain.2010.12.020 | s2cid = 140204185 }}
• Mosapride
• Prucalopride
• Renzapride
• RS-67506
• RS-67333{{snd}} partial agonist
• SL65.0155{{snd}} partial agonist
• Tegaserod
• Zacopride
• Metoclopramide
• Sulpiride
• Naronapride
• Usmarapride

• L-lysine
• Piboserod
• GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester){{cite journal | vauthors = Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP | title = GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor | journal = British Journal of Pharmacology | volume = 111 | issue = 1 | pages = 332–8 | date = January 1994 | pmid = 8012715 | pmc = 1910004 | doi = 10.1111/j.1476-5381.1994.tb14064.x }}
• GR-125,487
• RS-39604 (1-[4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1-[2-methylsulphonylamino]piperidin-4-yl]propan-1-one)
• SB-203,186
• SB-204,070
• ([Methoxy-¹¹C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate{{cite journal | vauthors = Xu R, Hong J, Morse CL, Pike VW | title = Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 19 | pages = 7035–47 | date = October 2010 | pmid = 20812727 | pmc = 2951497 | doi = 10.1021/jm100668r }}
• Chamomile (ethanol extract){{cite journal | vauthors = Simmen U, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D | year = 2006| title = Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors | journal = Phytomedicine| volume = 13| issue = Suppl 5| pages = 51–5| pmid = 16973340 | doi=10.1016/j.phymed.2006.03.012}}

• 5-HT receptor
• 5-HT₁ receptor
• 5-HT₂ receptor
• 5-HT₃ receptor
• 5-HT₅ receptor
• 5-HT₆ receptor
• 5-HT₇ receptor

{{Reflist|33em}}

{{Refbegin|33em}}

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{{Refend}}

• {{cite web| url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2329| title = 5-HT₄| work = IUPHAR Database of Receptors and Ion Channels| publisher = International Union of Basic and Clinical Pharmacology| access-date = 25 November 2008| archive-date = 5 June 2016| archive-url = https://web.archive.org/web/20160605115442/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2329| url-status = dead}}
• {{UCSC gene info|HTR4}}

{{NLM content}}

{{G protein-coupled receptors}}

{{Serotonergics}}

{{DEFAULTSORT:5-Ht4 Receptor}}

Category:Biology of bipolar disorder

Category:Serotonin receptors