5-HT4 receptor
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5-hydroxytryptamine (serotonin) receptor 4 | |||||||||||
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Identifiers | |||||||||||
Symbols | HTR4; 5-HT4; 5-HT4R | ||||||||||
External IDs | OMIM: 602164 MGI: 109246 HomoloGene: 20243 IUPHAR: 5-HT4 GeneCards: HTR4 Gene | ||||||||||
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RNA expression pattern | |||||||||||
More reference expression data | |||||||||||
Orthologs | |||||||||||
Species | Human | Mouse | |||||||||
Entrez | 3360 | 15562 | |||||||||
Ensembl | ENSG00000164270 | ENSMUSG00000026322 | |||||||||
UniProt | Q13639 | Q3URB5 | |||||||||
RefSeq (mRNA) | NM_000870 | NM_008313 | |||||||||
RefSeq (protein) | NP_000861 | NP_032339 | |||||||||
Location (UCSC) | Chr 5: 147.81 - 148.01 Mb | Chr 18: 62.45 - 62.59 Mb | |||||||||
PubMed search | [1] | [2] |
5-hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.[1][2]
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.[3]
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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 and pontine nuclei and some areas of the thalamus.It has not been found in the cerebellum.[5]
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, metoclopramide, renzapride and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.[6]
SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT4 in positron emission tomography pig[7]and human[8]studies.
Agonists
- BIMU-8
- Cisapride
- CJ-033,466
- Mosapride
- Prucalopride
- Renzapride
- RS-67506
- RS-67333 - partial agonist
- Tegaserod
- Zacopride
Antagonists
- Piboserod
- GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)[9]
- 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
See also
References
- ^ Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A, Taviaux S (December 1997). [Expression error: Missing operand for > "Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31→q33 by in situ hybridization."]. Cytogenet Cell Genet 78 (2): 133–4. doi: . PMID 9371406.
- ^ , Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (September 1997). [Expression error: Missing operand for > "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium."]. FEBS Lett 412 (3): 465–74. doi: . PMID 9276448.
- ^ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3360.
- ^ S. S. Hegde; R. M. Eglen (1 October 1996). "Peripheral 5-HT4 receptors". The FASEB journal 10 (12): 1398–1407. PMID 8903510. http://www.fasebj.org/cgi/content/abstract/10/12/1398.
- ^ Katarina Varnäs; Christer Halldin; Victor W. Pike; Håkan Hall (2003). [Expression error: Missing operand for > "Distribution of 5-HT4 receptors in the postmortem human brain—an autoradiographic study using [125]SB 207710"]. European Neuropsychopharmacology 13: 228–234. doi: .
- ^ Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L (April 2009). [Expression error: Missing operand for > "Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors"]. Molecular Pharmacology 75 (4): 982–90. doi: . PMID 19168624.
- ^ B. R. Kornum, N. M. Lind, N. Gillings, Lisbeth Marner, F. Andersen, Gitte Moos Knudsen (September 2008). [Expression error: Missing operand for > "Evaluation of the novel 5-HT(4) receptor PET ligand [(11)C]SB207145 in the Gottingen minipig"]. Journal of Cerebral Blood Flow and Metabolism 29 (1): 186. doi: . PMID 18797470.
- ^ 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) (Supplement 2): 159P. http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/48/MeetingAbstracts_2/159P.
- ^ 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
External links
- "5-HT4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2329.
Further reading
- Cecilie Löe Licht, Changes in the 5-HT4 receptor in animal models of depression and antidepressant treatment, PhD thesis, Faculty of Health Sciences, University of Copenhagen. Submitted 2008 October.
- Ullmer C, Schmuck K, Kalkman HO, Lübbert H (1995). [Expression error: Missing operand for > "Expression of serotonin receptor mRNAs in blood vessels."]. FEBS Lett. 370 (3): 215–21. doi: . PMID 7656980.
- Blondel O, Vandecasteele G, Gastineau M, et al. (1997). [Expression error: Missing operand for > "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium."]. FEBS Lett. 412 (3): 465–74. doi: . PMID 9276448.
- Van den Wyngaert I, Gommeren W, Verhasselt P, et al. (1997). [Expression error: Missing operand for > "Cloning and expression of a human serotonin 5-HT4 receptor cDNA."]. J. Neurochem. 69 (5): 1810–9. PMID 9349523.
- Claeysen S, Faye P, Sebben M, et al. (1997). [Expression error: Missing operand for > "Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase."]. Neuroreport 8 (15): 3189–96. doi: . PMID 9351641.
- Blondel O, Gastineau M, Dahmoune Y, et al. (1998). [Expression error: Missing operand for > "Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus."]. J. Neurochem. 70 (6): 2252–61. PMID 9603189.
- Cichon S, Kesper K, Propping P, Nöthen MM (1998). [Expression error: Missing operand for > "Assignment of the human serotonin 4 receptor gene (HTR4) to the long arm of chromosome 5 (5q31-q33)."]. Mol. Membr. Biol. 15 (2): 75–8. doi: . PMID 9724925.
- Claeysen S, Sebben M, Becamel C, et al. (1999). [Expression error: Missing operand for > "Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain."]. Mol. Pharmacol. 55 (5): 910–20. PMID 10220570.
- Bender E, Pindon A, van Oers I, et al. (2000). [Expression error: Missing operand for > "Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant."]. J. Neurochem. 74 (2): 478–89. doi: . PMID 10646498.
- Mialet J, Berque-Bestel I, Eftekhari P, et al. (2000). [Expression error: Missing operand for > "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."]. Br. J. Pharmacol. 129 (4): 771–81. doi: . PMID 10683202.
- Bach T, Syversveen T, Kvingedal AM, et al. (2001). [Expression error: Missing operand for > "5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle."]. Naunyn Schmiedebergs Arch. Pharmacol. 363 (2): 146–60. doi: . PMID 11218067.
- Medhurst AD, Lezoualc'h F, Fischmeister R, et al. (2001). [Expression error: Missing operand for > "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 Res. Mol. Brain Res. 90 (2): 125–34. doi: . PMID 11406291.
- Hiroi T, Hayashi-Kobayashi N, Nagumo S, et al. (2002). [Expression error: Missing operand for > "Identification and characterization of the human serotonin-4 receptor gene promoter."]. Biochem. Biophys. Res. Commun. 289 (2): 337–44. doi: . PMID 11716477.
- Vilaró MT, Doménech T, Palacios JM, Mengod G (2002). [Expression error: Missing operand for > "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: . PMID 11750916.
- López-Rodríguez ML, Murcia M, Benhamú B, et al. (2002). [Expression error: Missing operand for > "Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin."]. J. Comput. Aided Mol. Des. 15 (11): 1025–33. doi: . PMID 11989623.
- Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, et al. (2003). [Expression error: Missing operand for > "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees."]. Mol. Psychiatry 7 (9): 954–61. doi: . PMID 12399948.
- Norum JH, Hart K, Levy FO (2003). [Expression error: Missing operand for > "Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a)."]. J. Biol. Chem. 278 (5): 3098–104. doi: . PMID 12446729.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). [Expression error: Missing operand for > "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences."]. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi: . PMID 12477932.
- Cartier D, Lihrmann I, Parmentier F, et al. (2003). [Expression error: Missing operand for > "Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome."]. J. Clin. Endocrinol. Metab. 88 (1): 248–54. doi: . PMID 12519861.
- Manzke T, Guenther U, Ponimaskin EG, et al. (2003). [Expression error: Missing operand for > "5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia."]. Science 301 (5630): 226–9. doi: . PMID 12855812.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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