Thecholecystokinin B receptor also known asCCKBR orCCK2 is aprotein[5] that in humans is encoded by theCCKBRgene.[6]
This gene encodes aG protein-coupled receptor forgastrin andcholecystokinin (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]
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 ofdopamine activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing thedopamine-enhancing effects ofCCK-A. However, the effects of CCK-B ondopamine activity vary depending on location.[11] CCK-B antagonism enhances dopamine release in rat striatum.[12] Activation enhancesGABA release in rat anteriornucleus accumbens.[13] CCK-B receptors modulate dopamine release, and influence the development of tolerance toopioids.[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 ofcocaine-inducedconditioned place preference, and prevents the long-term maintenance and reinstatement ofmorphine-induced CPP.[16] Blockade of CCK-B potentiates cocaine-induced dopamine overflow in rat striatum.[12] CCK-B may pose a modulatory role inParkinson's disease. Blockade of CCK-B in dopamine-depletedsquirrel monkeys induces significant enhancement oflocomotor response toL-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]
^Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, et al. (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.PMID15001692.
^Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, et al. (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.PMID12695525.S2CID38395309.
^abLoonam 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.PMID12801594.
^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.PMID10651144.S2CID25668780.
^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.PMID2311658.
^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.PMID7972279.S2CID30502684.
^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.PMID11173090.S2CID23094648.
^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.PMID1976438.
^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.PMID12777967.
Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T (Oct 1994). "Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene".Cell Growth & Differentiation.5 (10):1127–35.PMID7848914.
Miyake A (Mar 1995). "A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon".Biochemical and Biophysical Research Communications.208 (1):230–7.doi:10.1006/bbrc.1995.1328.PMID7887934.
Maruyama K, Sugano S (Jan 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.PMID8125298.
Zimonjic DB, Popescu NC, Matsui T, Ito M, Chihara K (1993). "Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5→p15.4 by fluorescence in situ hybridization".Cytogenetics and Cell Genetics.65 (3):184–5.doi:10.1159/000133628.PMID8222757.
Beinborn M, Lee YM, McBride EW, Quinn SM, Kopin AS (Mar 1993). "A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists".Nature.362 (6418):348–50.Bibcode:1993Natur.362..348B.doi:10.1038/362348a0.PMID8455720.S2CID4344412.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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.PMID9373149.
O'Briant KC, Ali SY, Weier HU, Bepler G (Aug 1998). "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 Research.6 (5):415–8.doi:10.1023/A:1009289625352.PMID9872672.S2CID28496235.
Monstein HJ, Nilsson I, Ellnebo-Svedlund K, Svensson SP (1999). "Cloning and characterization of 5'-end alternatively spliced human cholecystokinin-B receptor mRNAs".Receptors & Channels.6 (3):165–77.PMID10100325.
Kulaksiz H, Arnold R, Göke B, Maronde E, Meyer M, Fahrenholz F, et al. (Feb 2000). "Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach".Cell and Tissue Research.299 (2):289–98.doi:10.1007/s004410050027 (inactive 11 July 2025).PMID10741470.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
