Cholecystokinin B receptor

CCKBR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1L4T
Identifiers
Aliases	CCKBR , CCK-B, CCK2R, GASR, cholecystokinin B receptor
External IDs	OMIM: 118445; MGI: 99479; HomoloGene: 7258; GeneCards: CCKBR; OMA:CCKBR - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11p15.4 Start 6,259,806 bp [1] End 6,272,127 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 E3|7 55.86 cM Start 105,074,938 bp [2] End 105,120,105 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 10 frontal pole body of stomach paraflocculus of cerebellum right frontal lobe dorsolateral prefrontal cortex cingulate gyrus middle temporal gyrus anterior cingulate cortex Brodmann area 46 Top expressed in primary motor cortex perirhinal cortex piriform cortex prefrontal cortex entorhinal cortex Ileal epithelium primary visual cortex anterior amygdaloid area superior frontal gyrus inferior colliculi More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity 1-phosphatidylinositol-3-kinase regulator activity protein binding type B gastrin/cholecystokinin receptor binding gastrin receptor activity cholecystokinin receptor activity peptide hormone binding Cellular component integral component of membrane membrane plasma membrane Biological process gastric acid secretion positive regulation of cytosolic calcium ion concentration cell surface receptor signaling pathway positive regulation of cell population proliferation cell population proliferation digestive tract development signal transduction gland development regulation of phosphatidylinositol 3-kinase activity G protein-coupled receptor signaling pathway phospholipase C-activating G protein-coupled receptor signaling pathway cholecystokinin signaling pathway pH reduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 887 12426 Ensembl ENSG00000110148 ENSMUSG00000030898 UniProt P32239 P56481 RefSeq (mRNA) NM_176875 NM_001318029 NM_001363552 NM_007627 RefSeq (protein) NP_001304958 NP_795344 NP_001350481 NP_031653 Location (UCSC) Chr 11: 6.26 – 6.27 Mb Chr 7: 105.07 – 105.12 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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

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

The cholecystokinin B receptor is stimulated by CCK and gastrin in the stomach during digestion. ^[19]

Selective ligands

The cholecystokinin B receptor responds to a number of ligands.

Agonists

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

Antagonists

• 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

• Cholecystokinin receptor
• Cholecystokinin antagonist

References

1. GRCh38: Ensembl release 89: ENSG00000110148 – Ensembl, May 2017
2. 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, 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. PMID   15001692.
9. 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. PMID   12695525. S2CID   38395309.
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. 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.
19. Zeng Q, Ou L, Wang W, Guo DY (2020-03-06). "Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes". Frontiers in Endocrinology. 11: 112. doi: 10.3389/fendo.2020.00112 . PMC   7067705 . PMID   32210918.

Further reading

• 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 (1): 283–97. Bibcode:1994NYASA.713..283H. doi:10.1111/j.1749-6632.1994.tb44076.x. PMID   8185170. S2CID   30088015.
• 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. doi: 10.1016/S0021-9258(18)53076-3 . PMID   7681836.
• 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. PMID   7848914.
• 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. PMID   7887934.
• 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. PMID   8125298.
• 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. PMID   8222757.
• de Weerth A, Pisegna JR, Huppi K, Wank SA (Jul 1993). "Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor". Biochemical and Biophysical Research Communications. 194 (2): 811–8. doi:10.1006/bbrc.1993.1894. PMID   8343165.
• Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, et al. (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. doi: 10.1016/S0021-9258(17)46844-X . hdl: 20.500.14094/D1001304 . PMID   8349705.
• Song I, Brown DR, Wiltshire RN, Gantz I, Trent JM, Yamada T (Oct 1993). "The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs". Proceedings of the National Academy of Sciences of the United States of America. 90 (19): 9085–9. Bibcode:1993PNAS...90.9085S. doi: 10.1073/pnas.90.19.9085 . PMC   47506 . PMID   8415658.
• 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. PMID   8455720. S2CID   4344412.
• Silvente-Poirot S, Wank SA (Jun 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". The Journal of Biological Chemistry. 271 (25): 14698–706. doi: 10.1074/jbc.271.25.14698 . PMID   8663021.
• Tarasova NI, Wank SA, Hudson EA, Romanov VI, Czerwinski G, Resau JH, et al. (Feb 1997). "Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor". Cell and Tissue Research. 287 (2): 325–33. doi:10.1007/s004410050757. PMID   8995203. S2CID   25466418.
• 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. PMID   9373149.
• 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. PMID   9872672. S2CID   28496235.
• 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. PMID   10100325.
• Daulhac L, Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C (Jul 1999). "Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors". The Journal of Biological Chemistry. 274 (29): 20657–63. doi: 10.1074/jbc.274.29.20657 . PMID   10400698.
• Silvente-Poirot S, Escrieut C, Galès C, Fehrentz JA, Escherich A, Wank SA, et al. (Aug 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". The Journal of Biological Chemistry. 274 (33): 23191–7. doi: 10.1074/jbc.274.33.23191 . PMID   10438490.
• 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). PMID   10741470.

External links

• 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.