Biology:5-HT4 receptor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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] 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[8] and human[9] studies.

Agonists

Antagonists

  • L-lysine
  • Piboserod
  • GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)[12]
  • 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[13]
  • Chamomile (ethanol extract)[14]

See also

References

  1. ↑ "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. December 1997. doi:10.1159/000134646. PMID 9371406. https://hal.archives-ouvertes.fr/hal-02491196/file/1997%20CytoCellGen%20Claeysen.pdf. 
  2. ↑ "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Letters 412 (3): 465–74. August 1997. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448. 
  3. ↑ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3360. 
  4. ↑ "Peripheral 5-HT4 receptors". FASEB Journal 10 (12): 1398–407. October 1996. doi:10.1096/fasebj.10.12.8903510. PMID 8903510. 
  5. ↑ "Distribution of 5-HT4 receptors in the postmortem human brain--an autoradiographic study using [125I]SB 207710". European Neuropsychopharmacology 13 (4): 228–34. August 2003. doi:10.1016/S0924-977X(03)00009-9. PMID 12888181. 
  6. ↑ "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. March 2010. doi:10.1016/j.cellsig.2009.11.004. PMID 19922792. 
  7. ↑ "Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors". Molecular Pharmacology 75 (4): 982–90. April 2009. doi:10.1124/mol.108.053686. PMID 19168624. https://hal.archives-ouvertes.fr/hal-02483472/file/2009%20MolPharm%20Pellissier.pdf. 
  8. ↑ "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. January 2009. doi:10.1038/jcbfm.2008.110. PMID 18797470. 
  9. ↑ "Kinetic modeling of 11C-SB207145 binding to 5-HT4 receptors in the human brain in vivo". Journal of Nuclear Medicine 50 (6): 900–8. June 2009. doi:10.2967/jnumed.108.058552. PMID 19470850. 
  10. ↑ Costall, B.; Naylor, R. J. (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. https://pubmed.ncbi.nlm.nih.gov/8201242/. 
  11. ↑ "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. March 2011. doi:10.1016/j.pain.2010.12.020. PMID 21239110. 
  12. ↑ "GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor". British Journal of Pharmacology 111 (1): 332–8. January 1994. doi:10.1111/j.1476-5381.1994.tb14064.x. PMID 8012715. 
  13. ↑ "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. October 2010. doi:10.1021/jm100668r. PMID 20812727. 
  14. ↑ "Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors". Phytomedicine 13 (Suppl 5): 51–5. 2006. 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.




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