5-HT4 receptor
| HTR4 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process |
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| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) |
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| RefSeq (protein) |
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| Location (UCSC) | Chr 5: 148.45 – 148.68 Mb | Chr 18: 62.46 – 62.63 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.[5][6]
Function
This gene is a member of the family of human
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.[7]
Location
The receptor is located in the
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.[9]Isoforms
Internalization is isoform-specific.[10]
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.[11] Amongst these agonists prucalopride has >150-fold higher affinity for 5-HT4 receptors than for other receptors.
and human[13] studies.Agonists
- Tropisetron[14] – partial agonist
- BIMU-8
- Cisapride
- CJ-033,466– partial agonist
- ML-10302[15]
- Mosapride
- Prucalopride
- Renzapride
- RS-67506
- RS-67333– partial agonist
- SL65.0155– partial agonist
- Tegaserod
- Zacopride
- Metoclopramide
- Sulpiride
- Naronapride
Antagonists
- L-lysine
- Piboserod
- GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)[16]
- 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[17]
- Chamomile (ethanol extract)[18]
See also
- 5-HT receptor
- 5-HT1 receptor
- 5-HT2 receptor
- 5-HT3 receptor
- 5-HT5 receptor
- 5-HT6 receptor
- 5-HT7 receptor
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164270 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026322 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9371406.
- S2CID 23714426.
- ^ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4".
- S2CID 21596751.
- S2CID 27945284.
- PMID 19922792.
- S2CID 17957338.
- PMID 18797470.
- PMID 19470850.
- S2CID 36692776.
- S2CID 140204185.
- PMID 8012715.
- PMID 20812727.
- PMID 16973340.
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 (August 1995). "Expression of serotonin receptor mRNAs in blood vessels". FEBS Letters. 370 (3): 215–21. S2CID 9015835.
- Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (August 1997). "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Letters. 412 (3): 465–74. S2CID 23714426.
- Van den Wyngaert I, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W, Bender E (November 1997). "Cloning and expression of a human serotonin 5-HT4 receptor cDNA". Journal of Neurochemistry. 69 (5): 1810–9. S2CID 25269904.
- Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A (October 1997). "Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase" (PDF). NeuroReport. 8 (15): 3189–96. S2CID 20624532.
- Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R (June 1998). "Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus" (PDF). Journal of Neurochemistry. 70 (6): 2252–61. S2CID 24203530.
- 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. 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 (February 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. S2CID 33817190.
- 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 (February 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. PMID 10683202.
- Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann AJ, Levy FO (February 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. S2CID 27504006.
- Medhurst AD, Lezoualc'h F, Fischmeister R, Middlemiss DN, Sanger GJ (June 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. PMID 11406291.
- Hiroi T, Hayashi-Kobayashi N, Nagumo S, Ino M, Okawa Y, Aoba A, Matsui H (November 2001). "Identification and characterization of the human serotonin-4 receptor gene promoter". Biochemical and Biophysical Research Communications. 289 (2): 337–44. PMID 11716477.
- Vilaró MT, Doménech T, Palacios JM, Mengod G (January 2002). "S2CID 23722311.
- López-Rodríguez ML, Murcia M, Benhamú B, Olivella M, Campillo M, Pardo L (November 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. S2CID 23478175.
- 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. S2CID 21064320.
- Norum JH, Hart K, Levy FO (January 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. 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 (January 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. PMID 12519861.
- Manzke T, Guenther U, Ponimaskin EG, Haller M, Dutschmann M, Schwarzacher S, Richter DW (July 2003). "5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia". Science. 301 (5630): 226–9. S2CID 13641423.
External links
- "5-HT4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Human HTR4 genome location and HTR4 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.