Cholecystokinin B receptor

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Cholecystokinin B receptor
250px NMR structure of the third extracellular loop of the human CCK-B receptor. PDB rendering based on 1l4t.
Available structures PDB 1l4t
Identifiers
Symbols	CCKBR; CCK-B; GASR
External IDs	OMIM: 118445 MGI: 99479 HomoloGene: 7258 IUPHAR: CCK2 GeneCards: CCKBR Gene
Gene Ontology Molecular function • rhodopsin-like receptor activity • phosphoinositide phospholipase C activity • receptor activity • gastrin receptor activity • phosphatidylinositol 3-kinase regulator activity Cellular component • plasma membrane • integral to plasma membrane Biological process • phospholipase C activation • elevation of cytosolic calcium ion concentration • digestion • sensory perception • feeding behavior • cell proliferation • positive regulation of cell proliferation Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	887	12426
Ensembl	ENSG00000110148	ENSMUSG00000030898
UniProt	P32239	Q3ZB46
RefSeq (mRNA)	NM_176875	NM_007627
RefSeq (protein)	NP_795344	NP_031653
Location (UCSC)	Chr 11: 6.24 - 6.25 Mb	Chr 7: 105.3 - 105.34 Mb
PubMed search	[1]	[2]

The cholecystokinin B receptor also known as CCKBR or CCK₂ is a protein that in humans is encoded by the CCKBR gene.

This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin (CCK), regulatory peptides of the brain and gastrointestinal tract. This protein is a type B gastrin receptor, which has a high affinity for both sulfated and nonsulfated CCK analogs and is found principally in the central nervous system and the gastrointestinal tract. A misspliced transcript variant including an intron has been observed in cells from colorectal and pancreatic tumors.

CNS effects

CCK receptors significantly influence neurotransmission in the brain, regulating anxiety, feeding, and locomotion. CCK-B expression may correlate parallel to anxiety and depression phenotypes in humans. CCK-B receptors possess a complex regulation of dopamine activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing the dopamine-enhancing effects of CCK-A. However, the effects of CCK-B on dopamine activity vary depending on location. CCK-B antagonism enhances dopamine release in rat striatum. Activation enhances GABA release in rat anterior nucleus accumbens. CCK-B receptors modulate dopamine release, and influence the development of tolerance to opioids. CCK-B activation decreases amphetamine-induced DA release, and contributes to individual variability in response to amphetamine.

In rats, CCK-B antagonism prevents the stress-induced reactivation of cocaine-induced conditioned place preference, and prevents the long-term maintenance and reinstatement of morphine-induced CPP. Blockade of CCK-B potentiates cocaine-induced dopamine overflow in rat striatum. CCK-B may pose a modulatory role in parkinson's disease. Blockade of CCK-B in dopamine-depleted squirrel monkeys induces significant enhancement of locomotor response to L-DOPA.

Selective Ligands

Agonists

• Cholecystokinin
• CCK-4
• Gastrin
• BBL-454

Antagonists

• Proglumide
• CI-988
• CI-1015
• L-365,260
• L-369,293
• YF-476
• YM-022
• RP-69758
• LY-225,910
• LY-288,513
• PD-135,158
• PD-145,942

Inverse agonists

• L-740,093

See also

• Cholecystokinin receptor
• Cholecystokinin antagonist

Further reading

• Herget T, Sethi T, Wu SV; et al. (1994). "Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors". Ann. N. Y. Acad. Sci. 713: 283–97. doi:10.1111/j.1749-6632.1994.tb44076.x. PMID 8185170. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Lee YM, Beinborn M, McBride EW; et al. (1993). "The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization". J. Biol. Chem. 268 (11): 8164–9. PMID 7681836. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ito M, Iwata N, Taniguchi T; et al. (1995). "Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene". Cell Growth Differ. 5 (10): 1127–35. PMID 7848914. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Miyake A (1995). "A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon". Biochem. Biophys. Res. Commun. 208 (1): 230–7. doi:10.1006/bbrc.1995.1328. PMID 7887934. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Zimonjic DB, Popescu NC, Matsui T; et al. (1993). "Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5→p15.4 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 65 (3): 184–5. doi:10.1159/000133628. PMID 8222757. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. doi:10.1006/bbrc.1993.1894. PMID 8343165. CS1 maint: Multiple names: authors list (link)
• Ito M, Matsui T, Taniguchi T; et al. (1993). "Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin". J. Biol. Chem. 268 (24): 18300–5. PMID 8349705. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Song I, Brown DR, Wiltshire RN; et al. (1993). "The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs". Proc. Natl. Acad. Sci. U.S.A. 90 (19): 9085–9. doi:10.1073/pnas.90.19.9085. PMC 47506 Freely accessible. PMID 8415658. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Beinborn M, Lee YM, McBride EW; et al. (1993). "A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists". Nature. 362 (6418): 348–50. doi:10.1038/362348a0. PMID 8455720. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Silvente-Poirot S, Wank SA (1996). "A segment of five amino acids in the second extracellular loop of the cholecystokinin-B receptor is essential for selectivity of the peptide agonist gastrin". J. Biol. Chem. 271 (25): 14698–706. doi:10.1074/jbc.271.25.14698. PMID 8663021. 
• Tarasova NI, Wank SA, Hudson EA; et al. (1997). "Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor". Cell Tissue Res. 287 (2): 325–33. doi:10.1007/s004410050757. PMID 8995203. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• O'Briant KC, Ali SY, Weier HU, Bepler G (1999). "An 84-kilobase physical map and repeat polymorphisms of the gastrin/cholecystokinin brain receptor region at the junction of chromosome segments 11p15.4 and 15.5". Chromosome Res. 6 (5): 415–8. doi:10.1023/A:1009289625352. PMID 9872672. CS1 maint: Multiple names: authors list (link)
• Monstein HJ, Nilsson I, Ellnebo-Svedlund K, Svensson SP (1999). "Cloning and characterization of 5'-end alternatively spliced human cholecystokinin-B receptor mRNAs". Recept. Channels. 6 (3): 165–77. PMID 10100325. CS1 maint: Multiple names: authors list (link)
• Daulhac L, Kowalski-Chauvel A, Pradayrol L; et al. (1999). "Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors". J. Biol. Chem. 274 (29): 20657–63. doi:10.1074/jbc.274.29.20657. PMID 10400698. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Silvente-Poirot S, Escrieut C, Galès C; et al. (1999). "Evidence for a direct interaction between the penultimate aspartic acid of cholecystokinin and histidine 207, located in the second extracellular loop of the cholecystokinin B receptor". J. Biol. Chem. 274 (33): 23191–7. doi:10.1074/jbc.274.33.23191. PMID 10438490. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kulaksiz H, Arnold R, Göke B; et al. (2000). "Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach". Cell Tissue Res. 299 (2): 289–98. doi:10.1007/s004410050027. PMID 10741470. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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