HTR4
Identifiers
AliasesHTR4, 5-HT4, 5-HT4R, 5-HT4 receptor, 5-hydroxytryptamine receptor 4
External IDsOMIM: 602164 MGI: 109246 HomoloGene: 20243 GeneCards: HTR4
Orthologs
SpeciesHumanMouse
Entrez

3360

15562

Ensembl

ENSG00000164270

ENSMUSG00000026322

UniProt

Q13639

P97288

RefSeq (mRNA)

NM_008313
NM_001364956
NM_001364957
NM_001364958
NM_001364959

RefSeq (protein)

NP_032339
NP_001351885
NP_001351886
NP_001351887
NP_001351888

Location (UCSC)Chr 5: 148.45 – 148.68 MbChr 18: 62.46 – 62.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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 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.[7]

Location

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS).[8] 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.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT4 in positron emission tomography pig[12] and human[13] studies.

Agonists

Antagonists

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164270 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026322 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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" (PDF). Cytogenetics and Cell Genetics. 78 (2): 133–4. doi:10.1159/000134646. PMID 9371406.
  6. ^ 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. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448. S2CID 23714426.
  7. ^ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4".
  8. ^ Hegde SS, Eglen RM (October 1996). "Peripheral 5-HT4 receptors". FASEB Journal. 10 (12): 1398–407. doi:10.1096/fasebj.10.12.8903510. PMID 8903510. S2CID 21596751.
  9. ^ Varnäs K, Halldin C, Pike VW, Hall H (August 2003). "Distribution of 5-HT4 receptors in the postmortem human brain--an autoradiographic study using [125I]SB 207710". European Neuropsychopharmacology. 13 (4): 228–34. doi:10.1016/S0924-977X(03)00009-9. PMID 12888181. S2CID 27945284.
  10. ^ Mnie-Filali O, Amraei MG, Benmbarek S, Archer-Lahlou E, Peñas-Cazorla R, Vilaró MT, Boye SM, Piñeyro G (March 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.
  11. ^ 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" (PDF). Molecular Pharmacology. 75 (4): 982–90. doi:10.1124/mol.108.053686. PMID 19168624. S2CID 17957338.
  12. ^ Kornum BR, Lind NM, Gillings N, Marner L, Andersen F, Knudsen GM (January 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.
  13. ^ Marner L, Gillings N, Comley RA, Baaré WF, Rabiner EA, Wilson AA, Houle S, Hasselbalch SG, Svarer C, Gunn RN, Laruelle M, Knudsen GM (June 2009). "Kinetic modeling of 11C-SB207145 binding to 5-HT4 receptors in the human brain in vivo". Journal of Nuclear Medicine. 50 (6): 900–8. doi:10.2967/jnumed.108.058552. PMID 19470850.
  14. ^ Costall B, Naylor RJ (November 1993). "The pharmacology of the 5-HT4 receptor". International Clinical Psychopharmacology. 8 (Suppl 2): 11–18. doi:10.1097/00004850-199311002-00002. ISSN 0268-1315. PMID 8201242. S2CID 36692776.
  15. ^ 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. S2CID 140204185.
  16. ^ Gale JD, Grossman CJ, Whitehead JW, Oxford AW, Bunce KT, Humphrey PP (January 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.
  17. ^ 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". Journal of Medicinal Chemistry. 53 (19): 7035–47. doi:10.1021/jm100668r. PMC 2951497. PMID 20812727.
  18. ^ Simmen U, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D (2006). "Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors". Phytomedicine. 13 (Suppl 5): 51–5. doi:10.1016/j.phymed.2006.03.012. PMID 16973340.

Further reading

External links

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


Cell surface receptor: G protein-coupled receptors
Serotonin receptor modulators
Categories