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Cholecystokinin A receptor

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The Cholecystokinin A receptor is a human protein, also known as CCKAR or CCK1, with CCK1 now being the IUPHAR-recommended name.

This gene encodes a G-protein coupled receptor that binds non-sulfated members of the cholecystokinin (CCK) family of peptide hormones. This receptor is a major physiologic mediator of pancreatic enzyme secretion and smooth muscle contraction of the gallbladder and stomach. In the central and peripheral nervous system this receptor regulates satiety and the release of beta-endorphin and dopamine.[1]

The extracellular, N-terminal, domain of this protein adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop. It is required for interaction of the cholecystokinin A receptor with its corresponding hormonal ligand.[2]

Selective Ligands

Agonists

  • Cholecystokinin
  • CCK-4
  • SR-146,131
  • A-71623 - modified tetrapeptide, potent and selective CCKA agonist, IC50 3.7nM, 1200x selectivity over CCKB, CAS# 130408-77-4

Antagonists

See also

References

  1. Entrez Gene: CCKAR cholecystokinin A receptor.
  2. Pellegrini M, Mierke DF (November 1999). Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy. Biochemistry 38 (45): 14775–83.

External links

Further reading


  • Varga G, Bálint A, Burghardt B, D'Amato M (2004). Involvement of endogenous CCK and CCK1 receptors in colonic motor function.. Br. J. Pharmacol. 141 (8): 1275–84.
  • Miller LJ, Holicky EL, Ulrich CD, Wieben ED (1995). Abnormal processing of the human cholecystokinin receptor gene in association with gallstones and obesity.. Gastroenterology 109 (4): 1375–80.
  • Huppi K, Siwarski D, Pisegna JR, Wank S (1995). Chromosomal localization of the gastric and brain receptors for cholecystokinin (CCKAR and CCKBR) in human and mouse.. Genomics 25 (3): 727–9.
  • de Weerth A, Pisegna JR, Huppi K, Wank SA (1993). Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor.. Biochem. Biophys. Res. Commun. 194 (2): 811–8.
  • Ulrich CD, Ferber I, Holicky E, et al. (1993). Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor.. Biochem. Biophys. Res. Commun. 193 (1): 204–11.
  • Kennedy K, Gigoux V, Escrieut C, et al. (1997). Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin.. J. Biol. Chem. 272 (5): 2920–6.
  • Inoue H, Iannotti CA, Welling CM, et al. (1997). Human cholecystokinin type A receptor gene: cytogenetic localization, physical mapping, and identification of two missense variants in patients with obesity and non-insulin-dependent diabetes mellitus (NIDDM).. Genomics 42 (2): 331–5.
  • Gigoux V, Escrieut C, Silvente-Poirot S, et al. (1998). Met-195 of the cholecystokinin-A receptor interacts with the sulfated tyrosine of cholecystokinin and is crucial for receptor transition to high affinity state.. J. Biol. Chem. 273 (23): 14380–6.
  • Funakoshi A, Fukamizu Y, Miyasaka K (2000). Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.. Digestion 60 Suppl 1: 75–80.
  • Gigoux V, Escrieut C, Fehrentz JA, et al. (1999). Arginine 336 and asparagine 333 of the human cholecystokinin-A receptor binding site interact with the penultimate aspartic acid and the C-terminal amide of cholecystokinin.. J. Biol. Chem. 274 (29): 20457–64.
  • Gigoux V, Maigret B, Escrieut C, et al. (2000). Arginine 197 of the cholecystokinin-A receptor binding site interacts with the sulfate of the peptide agonist cholecystokinin.. Protein Sci. 8 (11): 2347–54.
  • Funakoshi A, Miyasaka K, Matsumoto H, et al. (2000). Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism.. FEBS Lett. 466 (2–3): 264–6.
  • Tachikawa H, Harada S, Kawanishi Y, et al. (2000). Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia. Am. J. Med. Genet. 96 (2): 141–5.
  • Giragossian C, Mierke DF (2001). Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin A receptor. Biochemistry 40 (13): 3804–9.
  • Schmitz F, Schrader H, Otte J, et al. (2002). Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells. Regul. Pept. 101 (1–3): 25–33.
  • Tachikawa H, Harada S, Kawanishi Y, et al. (2002). Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia. Psychiatry Research 103 (2–3): 147–55.
  • Schmitz F, Göke MN, Otte JM, et al. (2002). Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa. Regul. Pept. 102 (2–3): 101–10.
  • Okubo T, Harada S, Higuchi S, Matsushita S (2003). Investigation of quantitative trait loci in the CCKAR gene with susceptibility to alcoholism. Alcohol. Clin. Exp. Res. 26 (8 Suppl): 2S–5S.
  • Takata Y, Takeda S, Kawanami T, et al. (2003). Promoter analysis of human cholecystokinin type-A receptor gene. J. Gastroenterol. 37 (10): 815–20.




This article incorporates text from the United States National Library of Medicine, which is in the public domain.Template:Transmembranereceptor-stub Template:PDB Gallery


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