5-HT4 receptor

5-hydroxytryptamine (serotonin) receptor 4, also known as HTR4, is a human gene.

PBB_Summary
section_title =
summary_text = This gene is a member of the family of 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 = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3360| accessdate = ]

Ligands

Several drugs which act as 5-HT₄ selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs which act as 5-HT₄ agonists are also active as 5-HT₃ antagonists, such as mosapride, renzapride and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT₄ in positron emission tomography pig [Cite journal
author = B. R. Kornum, N. M. Lind, N. Gillings, Lisbeth Marner, F. Andersen, Gitte Moos Knudsen
title = Evaluation of the novel 5-HT(4) receptor PET ligand (11)CSB207145 in the Gottingen minipig
journal = Journal of Cerebral Blood Flow and Metabolism
year = 2008
month = September
doi = 10.1038/jcbfm.2008.110
pmid = 18797470] and human [Cite journal
title = Quantification of 11C-SB207145-PET for 5-HT4 receptors in the human brain: Preliminary results
author = Lisbeth Marner, Nic Gillings, Roger Gunn, Robert Comley, William Baaré, Steen Hasselbalch and Gitte Knudsen
journal = Journal of Nuclear Medicine
year = 2008
volume = 48 (Supplement 2)
pages = 159P
url = http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/48/MeetingAbstracts_2/159P] studies.

Agonists

*BIMU-8
*Cisapride
*Mosapride
*Renzapride
*Tegaserod
*Zacopride
*RS 67333 - partial agonist

Antagonists

*Piboserod
*GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1- [2- [(methylsulfonyl)amino] ethyl] -4-piperidinyl] methyl ester) [Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP. GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor. "British Journal of Pharmacology". 1994 Jan;111(1):332-8. PMID 8012715]
*RS-39604 (1- [4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy] -3- [1- [2-methylsulphonylamino] ethyl] piperidin-4-yl] propan-1-one)

ee also

* 5-HT receptor

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Ullmer C, Schmuck K, Kalkman HO, Lübbert H |title=Expression of serotonin receptor mRNAs in blood vessels. |journal=FEBS Lett. |volume=370 |issue= 3 |pages= 215–21 |year= 1995 |pmid= 7656980 |doi=
*cite journal | author=Blondel O, Vandecasteele G, Gastineau M, "et al." |title=Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium. |journal=FEBS Lett. |volume=412 |issue= 3 |pages= 465–74 |year= 1997 |pmid= 9276448 |doi=
*cite journal | author=Van den Wyngaert I, Gommeren W, Verhasselt P, "et al." |title=Cloning and expression of a human serotonin 5-HT4 receptor cDNA. |journal=J. Neurochem. |volume=69 |issue= 5 |pages= 1810–9 |year= 1997 |pmid= 9349523 |doi=
*cite journal | author=Claeysen S, Faye P, Sebben M, "et al." |title=Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase. |journal=Neuroreport |volume=8 |issue= 15 |pages= 3189–96 |year= 1997 |pmid= 9351641 |doi=
*cite journal | author=Claeysen S, Faye P, Sebben M, "et al." |title=Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31-->q33 by in situ hybridization. |journal=Cytogenet. Cell Genet. |volume=78 |issue= 2 |pages= 133–4 |year= 1997 |pmid= 9371406 |doi=
*cite journal | author=Blondel O, Gastineau M, Dahmoune Y, "et al." |title=Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus. |journal=J. Neurochem. |volume=70 |issue= 6 |pages= 2252–61 |year= 1998 |pmid= 9603189 |doi=
*cite journal | author=Cichon S, Kesper K, Propping P, Nöthen MM |title=Assignment of the human serotonin 4 receptor gene (HTR4) to the long arm of chromosome 5 (5q31-q33). |journal=Mol. Membr. Biol. |volume=15 |issue= 2 |pages= 75–8 |year= 1998 |pmid= 9724925 |doi=
*cite journal | author=Claeysen S, Sebben M, Becamel C, "et al." |title=Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. |journal=Mol. Pharmacol. |volume=55 |issue= 5 |pages= 910–20 |year= 1999 |pmid= 10220570 |doi=
*cite journal | author=Bender E, Pindon A, van Oers I, "et al." |title=Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. |journal=J. Neurochem. |volume=74 |issue= 2 |pages= 478–89 |year= 2000 |pmid= 10646498 |doi=
*cite journal | author=Mialet J, Berque-Bestel I, Eftekhari P, "et al." |title=Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines. |journal=Br. J. Pharmacol. |volume=129 |issue= 4 |pages= 771–81 |year= 2000 |pmid= 10683202 |doi= 10.1038/sj.bjp.0703101
*cite journal | author=Bach T, Syversveen T, Kvingedal AM, "et al." |title=5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. |journal=Naunyn Schmiedebergs Arch. Pharmacol. |volume=363 |issue= 2 |pages= 146–60 |year= 2001 |pmid= 11218067 |doi=
*cite journal | author=Medhurst AD, Lezoualc'h F, Fischmeister R, "et al." |title=Quantitative mRNA analysis of five C-terminal splice variants of the human 5-HT4 receptor in the central nervous system by TaqMan real time RT-PCR. |journal=Brain Res. Mol. Brain Res. |volume=90 |issue= 2 |pages= 125–34 |year= 2001 |pmid= 11406291 |doi=
*cite journal | author=Hiroi T, Hayashi-Kobayashi N, Nagumo S, "et al." |title=Identification and characterization of the human serotonin-4 receptor gene promoter. |journal=Biochem. Biophys. Res. Commun. |volume=289 |issue= 2 |pages= 337–44 |year= 2002 |pmid= 11716477 |doi= 10.1006/bbrc.2001.5979
*cite journal | author=Vilaró MT, Doménech T, Palacios JM, Mengod G |title=Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants. |journal=Neuropharmacology |volume=42 |issue= 1 |pages= 60–73 |year= 2002 |pmid= 11750916 |doi=
*cite journal | author=López-Rodríguez ML, Murcia M, Benhamú B, "et al." |title=Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin. |journal=J. Comput. Aided Mol. Des. |volume=15 |issue= 11 |pages= 1025–33 |year= 2002 |pmid= 11989623 |doi=
*cite journal | author=Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, "et al." |title=Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees. |journal=Mol. Psychiatry |volume=7 |issue= 9 |pages= 954–61 |year= 2003 |pmid= 12399948 |doi= 10.1038/sj.mp.4001133
*cite journal | author=Norum JH, Hart K, Levy FO |title=Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a). |journal=J. Biol. Chem. |volume=278 |issue= 5 |pages= 3098–104 |year= 2003 |pmid= 12446729 |doi= 10.1074/jbc.M206237200
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Cartier D, Lihrmann I, Parmentier F, "et al." |title=Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome. |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue= 1 |pages= 248–54 |year= 2003 |pmid= 12519861 |doi=
*cite journal | author=Manzke T, Guenther U, Ponimaskin EG, "et al." |title=5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. |journal=Science |volume=301 |issue= 5630 |pages= 226–9 |year= 2003 |pmid= 12855812 |doi= 10.1126/science.1084674

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