Cholecystokinin B receptor

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Protein CCKBR PDB 1l4t.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesCCKBR, CCK-B, CCK2R, GASR, cholecystokinin B receptor
External IDsOMIM: 118445 MGI: 99479 HomoloGene: 7258 GeneCards: CCKBR
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for CCKBR
Genomic location for CCKBR
Band11p15.4Start6,259,806 bp[1]
End6,272,127 bp[1]
RNA expression pattern
PBB GE CCKBR 210381 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 11: 6.26 – 6.27 MbChr 7: 105.43 – 105.47 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein[5] that in humans is encoded by the CCKBR gene.[6]

This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin (CCK),[7][8][9] 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.[10]

CNS effects[edit]

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.[11] CCK-B antagonism enhances dopamine release in rat striatum.[12] Activation enhances GABA release in rat anterior nucleus accumbens.[13] CCK-B receptors modulate dopamine release, and influence the development of tolerance to opioids.[14] CCK-B activation decreases amphetamine-induced DA release, and contributes to individual variability in response to amphetamine.[15]

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.[16] Blockade of CCK-B potentiates cocaine-induced dopamine overflow in rat striatum.[12] 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.[17] 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.[18]

Gastrointestinal Tract[edit]

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

Selective Ligands[edit]

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[edit]

  • L-740,093

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110148 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030898 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Noble F, Roques BP (Jul 1999). "CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology". Progress in Neurobiology. 58 (4): 349–79. doi:10.1016/S0301-0082(98)00090-2. PMID 10368033. S2CID 24402373.
  6. ^ Pisegna JR, de Weerth A, Huppi K, Wank SA (Nov 1992). "Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization". Biochemical and Biophysical Research Communications. 189 (1): 296–303. doi:10.1016/0006-291X(92)91557-7. PMC 6719700. PMID 1280419.
  7. ^ Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (Jan 2005). "Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy". The Journal of Biological Chemistry. 280 (2): 1044–50. doi:10.1074/jbc.M409480200. PMID 15520004.
  8. ^ Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (Mar 2004). "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". Journal of Nuclear Medicine. 45 (3): 485–94. PMID 15001692.
  9. ^ 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". Molecular Pharmacology. 63 (5): 973–82. doi:10.1124/mol.63.5.973. PMID 12695525.
  10. ^ "Entrez Gene: CCKBR cholecystokinin B receptor".
  11. ^ Altar CA, Boyar WC (Apr 1989). "Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin". Brain Research. 483 (2): 321–6. doi:10.1016/0006-8993(89)90176-5. PMID 2706523. S2CID 7306848.
  12. ^ a b Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (Jun 2003). "Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum". Life Sciences. 73 (6): 727–39. doi:10.1016/S0024-3205(03)00393-X. PMID 12801594.
  13. ^ Lanza M, Makovec F (Jan 2000). "Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons". Naunyn-Schmiedeberg's Archives of Pharmacology. 361 (1): 33–8. doi:10.1007/s002109900161. PMID 10651144. S2CID 25668780.
  14. ^ Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (Jan 1990). "The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat". European Journal of Pharmacology. 176 (1): 35–44. doi:10.1016/0014-2999(90)90129-T. PMID 2311658.
  15. ^ Higgins GA, Sills TL, Tomkins DM, Sellers EM, Vaccarino FJ (Aug 1994). "Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion". Pharmacology Biochemistry and Behavior. 48 (4): 1019–24. doi:10.1016/0091-3057(94)90214-3. PMID 7972279. S2CID 30502684.
  16. ^ Lu L, Huang M, Ma L, Li J (Apr 2001). "Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats". Behavioural Brain Research. 120 (1): 105–10. doi:10.1016/S0166-4328(00)00361-2. PMID 11173090. S2CID 23094648.
  17. ^ Boyce S, Rupniak NM, Tye S, Steventon MJ, Iversen SD (Aug 1990). "Modulatory role for CCK-B antagonists in Parkinson's disease". Clinical Neuropharmacology. 13 (4): 339–47. doi:10.1097/00002826-199008000-00009. PMID 1976438.
  18. ^ Wang J, Si YM, Liu ZL, Yu L (Jun 2003). "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease". Pharmacogenetics. 13 (6): 365–9. doi:10.1097/00008571-200306000-00008. PMID 12777967.

Further reading[edit]

External links[edit]

  • Overview of all the structural information available in the PDB for UniProt: P32239 (Gastrin/cholecystokinin type B receptor) at the PDBe-KB.

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