5-HT4 receptor

5-HT4 receptor

5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled
Identifiers
Symbols  ; 5-HT4; 5-HT4R
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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

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]

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

  • 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

References

  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.  
  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.  
  3. ^ "Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4". 
  4. ^ S. S. Hegde; R. M. Eglen (1 October 1996). "Peripheral 5-HT4 receptors".  
  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.  
  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.  
  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.  
  8. ^ B. R. Kornum, N. M. Lind, N. Gillings, Lisbeth Marner, F. Andersen,  
  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".  
  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.  
  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.  
  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.  
  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

  • "4"5-HT. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading

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



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