The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBRgene.
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.
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. 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.
^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. PMID15001692.
^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. PMID12695525.
^ 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.
Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E (Mar 1994). "Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors". Annals of the New York Academy of Sciences. 713: 283–97. doi:10.1111/j.1749-6632.1994.tb44076.x. PMID8185170. S2CID30088015.
Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF, Kopin AS (Apr 1993). "The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization". The Journal of Biological Chemistry. 268 (11): 8164–9. PMID7681836.
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.
Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K (Aug 1993). "Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin". The Journal of Biological Chemistry. 268 (24): 18300–5. PMID8349705.
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. 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, Forssmann WG, Eissele R (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. PMID10741470.