Open Access Articles- Top Results for Cholecystokinin B receptor

Cholecystokinin B receptor

External IDsOMIM118445 MGI99479 HomoloGene7258 IUPHAR: 77 ChEMBL: 298 GeneCards: CCKBR Gene
RNA expression pattern
File:PBB GE CCKBR 210381 s at tn.png
More reference expression data
RefSeq (mRNA)NM_176875NM_007627
RefSeq (protein)NP_795344NP_031653
Location (UCSC)Chr 11:
6.28 – 6.29 Mb
Chr 7:
105.43 – 105.47 Mb
PubMed search[1][2]

The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein[1] that in humans is encoded by the CCKBR gene.[2]

This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin (CCK),[3][4][5] 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.[6]

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.[7] CCK-B antagonism enhances dopamine release in rat striatum.[8] Activation enhances GABA release in rat anterior nucleus accumbens.[9] CCK-B receptors modulate dopamine release, and influence the development of tolerance to opioids.[10] CCK-B activation decreases amphetamine-induced DA release, and contributes to individual variability in response to amphetamine.[11]

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.[12] Blockade of CCK-B potentiates cocaine-induced dopamine overflow in rat striatum.[8] 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.[13] One study shows that visual hallucinations in Parkinson's disease are associated with cholecystokinin −45C>T polymorphism, and this association is still observed in the presence of the cholecystokinin-A receptor TC/CC genotype, indicating a possible interaction of these two genes in the visual hallucinogenesis in Parkinson's disease.[14]

Gastrointestinal Tract

The cholecystokinin B receptor is stimulated by CCK and gastrin in the stomach during digestion.

Selective Ligands

The cholecystokinin B receptor responds to a number of ligands.



  • Proglumide
  • CI-988
  • CI-1015
  • L-365,260
  • L-369,293
  • YF476
  • YM-022
  • RP-69758
  • LY-225,910
  • LY-288,513
  • PD-135,158
  • PD-145,942

Inverse agonists

  • L-740,093

See also


  1. ^ Noble F, Roques BP (July 1999). "CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology". Prog. Neurobiol. 58 (4): 349–79. PMID 10368033. doi:10.1016/S0301-0082(98)00090-2. 
  2. ^ Pisegna JR, de Weerth A, Huppi K, Wank SA (November 1992). "Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization". Biochem. Biophys. Res. Commun. 189 (1): 296–303. PMID 1280419. doi:10.1016/0006-291X(92)91557-7. 
  3. ^ Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (January 2005). "Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy". J. Biol. Chem. 280 (2): 1044–50. PMID 15520004. doi:10.1074/jbc.M409480200. 
  4. ^ Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (March 2004). "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". J. Nucl. Med. 45 (3): 485–94. PMID 15001692. 
  5. ^ Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, Escrieut C, Pradayrol L, Fourmy D, Silvente-Poirot S (May 2003). "Identification of tyrosine 189 and asparagine 358 of the cholecystokinin 2 receptor in direct interaction with the crucial C-terminal amide of cholecystokinin by molecular modeling, site-directed mutagenesis, and structure/affinity studies". Mol. Pharmacol. 63 (5): 973–82. PMID 12695525. doi:10.1124/mol.63.5.973. 
  6. ^ "Entrez Gene: CCKBR cholecystokinin B receptor". 
  7. ^ Altar CA, Boyar WC (April 1989). "Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin". Brain Res. 483 (2): 321–6. PMID 2706523. doi:10.1016/0006-8993(89)90176-5. 
  8. ^ a b Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (June 2003). "Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum". Life Sci. 73 (6): 727–39. PMID 12801594. doi:10.1016/S0024-3205(03)00393-X. 
  9. ^ Lanza M, Makovec F (January 2000). "Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons". Naunyn Schmiedebergs Arch. Pharmacol. 361 (1): 33–8. PMID 10651144. doi:10.1007/s002109900161. 
  10. ^ Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (January 1990). "The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat". Eur. J. Pharmacol. 176 (1): 35–44. PMID 2311658. doi:10.1016/0014-2999(90)90129-T. 
  11. ^ Higgins GA, Sills TL, Tomkins DM, Sellers EM, Vaccarino FJ (August 1994). "Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion". Pharmacol. Biochem. Behav. 48 (4): 1019–24. PMID 7972279. doi:10.1016/0091-3057(94)90214-3. 
  12. ^ Lu L, Huang M, Ma L, Li J (April 2001). "Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats". Behav. Brain Res. 120 (1): 105–10. PMID 11173090. doi:10.1016/S0166-4328(00)00361-2. 
  13. ^ Boyce S, Rupniak NM, Tye S, Steventon MJ, Iversen SD (August 1990). "Modulatory role for CCK-B antagonists in Parkinson's disease". Clin Neuropharmacol 13 (4): 339–47. PMID 1976438. doi:10.1097/00002826-199008000-00009. 
  14. ^ Wang J, Si YM, Liu ZL, Yu L. (June 2003). "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease.". Pharmacogenetics 13 (6): 365–9. PMID 12777967. doi:10.1097/00008571-200306000-00008. 

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. PMID 8185170. doi:10.1111/j.1749-6632.1994.tb44076.x. 
  • 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. 
  • 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. 
  • 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. PMID 7887934. doi:10.1006/bbrc.1995.1328. 
  • 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. PMID 8125298. doi:10.1016/0378-1119(94)90802-8. 
  • 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. PMID 8222757. doi:10.1159/000133628. 
  • 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. PMID 8343165. doi:10.1006/bbrc.1993.1894. 
  • 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. 
  • 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. PMC 47506. PMID 8415658. doi:10.1073/pnas.90.19.9085. 
  • 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. PMID 8455720. doi:10.1038/362348a0. 
  • 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. PMID 8663021. doi:10.1074/jbc.271.25.14698. 
  • 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. PMID 8995203. doi:10.1007/s004410050757. 
  • 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. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3. 
  • 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. PMID 9872672. doi:10.1023/A:1009289625352. 
  • 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. 
  • 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. PMID 10400698. doi:10.1074/jbc.274.29.20657. 
  • 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. PMID 10438490. doi:10.1074/jbc.274.33.23191. 
  • 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. PMID 10741470. doi:10.1007/s004410050027. 

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