5-HT4 receptor

5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled
Identifiers
Symbols HTR4 ; 5-HT4; 5-HT4R
External IDs OMIM: 602164 MGI: 109246 HomoloGene: 20243 IUPHAR: 9 ChEMBL: 1875 GeneCards: HTR4 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3360 15562
Ensembl ENSG00000164270 ENSMUSG00000026322
UniProt Q13639 P97288
RefSeq (mRNA) NM_000870 NM_008313
RefSeq (protein) NP_000861 NP_032339
Location (UCSC) Chr 5:
148.45 – 148.68 Mb		 Chr 18:
62.32 – 62.47 Mb
PubMed search

5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.[1][2]

Function

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.[3]

Location

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS).[4] 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.[5]

Isoforms

Internalization is isoform-specific.[6]

Ligands

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.[7]

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT4 in positron emission tomography pig[8] and human[9] studies.

Agonists

Antagonists

See also

References

  1. ↑ Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A, Taviaux S (December 1997). "Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31-->q33 by in situ hybridization". Cytogenetics and Cell Genetics 78 (2): 133–4. doi:10.1159/000134646. PMID 9371406.
  2. ↑ Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (Aug 1997). "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Letters 412 (3): 465–74. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448.
  3. ↑ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4".
  4. ↑ Hegde SS, Eglen RM (Oct 1996). "Peripheral 5-HT4 receptors". FASEB Journal 10 (12): 1398–407. PMID 8903510.
  5. ↑ Katarina Varnäs; Christer Halldin; Victor W. Pike; Håkan Hall (2003). "Distribution of 5-HT4 receptors in the postmortem human brain—an autoradiographic study using [125]SB 207710". European Neuropsychopharmacology 13 (4): 228–234. doi:10.1016/S0924-977X(03)00009-9.
  6. ↑ Mnie-Filali O, Amraei MG, Benmbarek S, Archer-Lahlou E, Peñas-Cazorla R, Vilaró MT, Boye SM, Piñeyro G (Mar 2010). "Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: effects of 5-HT and RS67333 on isoforms A and B". Cellular Signalling 22 (3): 501–9. doi:10.1016/j.cellsig.2009.11.004. PMID 19922792.
  7. ↑ Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L (Apr 2009). "Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors". Molecular Pharmacology 75 (4): 982–90. doi:10.1124/mol.108.053686. PMID 19168624.
  8. ↑ Kornum BR, Lind NM, Gillings N, Marner L, Andersen F, Knudsen GM (Jan 2009). "Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Göttingen minipig". Journal of Cerebral Blood Flow and Metabolism 29 (1): 186–96. doi:10.1038/jcbfm.2008.110. PMID 18797470.
  9. ↑ Lisbeth Marner, Nic Gillings, Roger Gunn, Robert Comley, William Baaré, Steen Hasselbalch and Gitte Knudsen (1 May 2008). "Quantification of 11C-SB207145-PET for 5-HT4 receptors in the human brain: Preliminary results". Journal of Nuclear Medicine 48 (Supplement 2): 159P.
  10. ↑ Godínez-Chaparro B, Barragán-Iglesias P, Castañeda-Corral G, Rocha-González HI, Granados-Soto V (Mar 2011). "Role of peripheral 5-HT(4), 5-HT(6), and 5-HT(7) receptors in development and maintenance of secondary mechanical allodynia and hyperalgesia". Pain 152 (3): 687–97. doi:10.1016/j.pain.2010.12.020. PMID 21239110.
  11. ↑ Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP (Jan 1994). "GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor". British Journal of Pharmacology 111 (1): 332–8. doi:10.1111/j.1476-5381.1994.tb14064.x. PMC 1910004. PMID 8012715.
  12. ↑ Xu R, Hong J, Morse CL, Pike VW (Oct 2010). "Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography". Journal of Medicinal Chemistry 53 (19): 7035–47. doi:10.1021/jm100668r. PMC 2951497. PMID 20812727.
  13. ↑ Simmen U, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D. "Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors."

Further reading

  • Licht CL, 2009, Changes in the 5-HT4 receptor in animal models of depression and antidepressant treatment, PhD thesis, University of Copenhagen.
  • Ullmer C, Schmuck K, Kalkman HO, Lübbert H (Aug 1995). "Expression of serotonin receptor mRNAs in blood vessels". FEBS Letters 370 (3): 215–21. doi:10.1016/0014-5793(95)00828-W. PMID 7656980. 
  • Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (Aug 1997). "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Letters 412 (3): 465–74. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448. 
  • Van den Wyngaert I, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W, Bender E (Nov 1997). "Cloning and expression of a human serotonin 5-HT4 receptor cDNA". Journal of Neurochemistry 69 (5): 1810–9. doi:10.1046/j.1471-4159.1997.69051810.x. PMID 9349523. 
  • Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A (Oct 1997). "Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase". Neuroreport 8 (15): 3189–96. doi:10.1097/00001756-199710200-00002. PMID 9351641. 
  • Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R (Jun 1998). "Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus". Journal of Neurochemistry 70 (6): 2252–61. doi:10.1046/j.1471-4159.1998.70062252.x. PMID 9603189. 
  • Cichon S, Kesper K, Propping P, Nöthen MM (1998). "Assignment of the human serotonin 4 receptor gene (HTR4) to the long arm of chromosome 5 (5q31-q33)". Molecular Membrane Biology 15 (2): 75–8. doi:10.3109/09687689809027521. PMID 9724925. 
  • Claeysen S, Sebben M, Becamel C, Bockaert J, Dumuis A (May 1999). "Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain". Molecular Pharmacology 55 (5): 910–20. PMID 10220570. 
  • Bender E, Pindon A, van Oers I, Zhang YB, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W (Feb 2000). "Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant". Journal of Neurochemistry 74 (2): 478–89. doi:10.1046/j.1471-4159.2000.740478.x. PMID 10646498. 
  • Mialet J, Berque-Bestel I, Eftekhari P, Gastineau M, Giner M, Dahmoune Y, Donzeau-Gouge P, Hoebeke J, Langlois M, Sicsic S, Fischmeister R, Lezoualc'h F (Feb 2000). "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". British Journal of Pharmacology 129 (4): 771–81. doi:10.1038/sj.bjp.0703101. PMC 1571890. PMID 10683202. 
  • Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann AJ, Levy FO (Feb 2001). "5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle". Naunyn-Schmiedeberg's Archives of Pharmacology 363 (2): 146–60. doi:10.1007/s002100000299. PMID 11218067. 
  • Medhurst AD, Lezoualc'h F, Fischmeister R, Middlemiss DN, Sanger GJ (Jun 2001). "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". Brain Research. Molecular Brain Research 90 (2): 125–34. doi:10.1016/S0169-328X(01)00095-X. PMID 11406291. 
  • Hiroi T, Hayashi-Kobayashi N, Nagumo S, Ino M, Okawa Y, Aoba A, Matsui H (Nov 2001). "Identification and characterization of the human serotonin-4 receptor gene promoter". Biochemical and Biophysical Research Communications 289 (2): 337–44. doi:10.1006/bbrc.2001.5979. PMID 11716477. 
  • Vilaró MT, Doménech T, Palacios JM, Mengod G (Jan 2002). "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". Neuropharmacology 42 (1): 60–73. doi:10.1016/S0028-3908(01)00154-X. PMID 11750916. 
  • López-Rodríguez ML, Murcia M, Benhamú B, Olivella M, Campillo M, Pardo L (Nov 2001). "Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin". Journal of Computer-Aided Molecular Design 15 (11): 1025–33. doi:10.1023/A:1014895611874. PMID 11989623. 
  • Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, Toyota T, Shimizu H, Yamada K, Yoshitsugu K, Hattori E, Yoshikawa T, Arinami T (2003). "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees". Molecular Psychiatry 7 (9): 954–61. doi:10.1038/sj.mp.4001133. PMID 12399948. 
  • Norum JH, Hart K, Levy FO (Jan 2003). "Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a)". The Journal of Biological Chemistry 278 (5): 3098–104. doi:10.1074/jbc.M206237200. PMID 12446729. 
  • Cartier D, Lihrmann I, Parmentier F, Bastard C, Bertherat J, Caron P, Kuhn JM, Lacroix A, Tabarin A, Young J, Vaudry H, Lefebvre H (Jan 2003). "Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome". The Journal of Clinical Endocrinology and Metabolism 88 (1): 248–54. doi:10.1210/jc.2002-021107. PMID 12519861. 
  • Manzke T, Guenther U, Ponimaskin EG, Haller M, Dutschmann M, Schwarzacher S, Richter DW (Jul 2003). "5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia". Science 301 (5630): 226–9. doi:10.1126/science.1084674. PMID 12855812. 

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia - version of the Friday, January 01, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.