5-HT4 receptor

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5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled
Identifiers
Symbols HTR4 ; 5-HT4; 5-HT4R
External IDs OMIM602164 MGI109246 HomoloGene20243 IUPHAR: 5-HT4 ChEMBL: 1875 GeneCards: HTR4 Gene
RNA expression pattern
PBB GE HTR4 216939 s at tn.png
PBB GE HTR4 207577 at tn.png
PBB GE HTR4 207578 s at tn.png
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:
147.83 – 148.06 Mb
Chr 18:
62.32 – 62.47 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 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[edit]

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[edit]

Internalization is isoform-specific.[6]

Ligands[edit]

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[edit]

Antagonists[edit]

  • Piboserod
  • GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)[11]
  • 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[12]
  • Chamomile (ethanol extract)[13]

See also[edit]

References[edit]

  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". Cytogenet Cell Genet 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 (September 1997). "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Lett 412 (3): 465–74. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448. 
  3. ^ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4". 
  4. ^ S. S. Hegde; R. M. Eglen (1 October 1996). "Peripheral 5-HT4 receptors". FASEB J. 10 (12): 1398–1407. 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, et al. (March 2010). "Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: effects of 5-HT and RS67333 on isoforms A and B". Cell. Signal. 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 (April 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. ^ B. R. Kornum, N. M. Lind, N. Gillings, Lisbeth Marner, F. Andersen, Gitte Moos Knudsen (September 2008). "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): 186–96. 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 (March 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 (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 (October 2010). "Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography". J. Med. Chem. 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."

External links[edit]

  • "5-HT4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading[edit]

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