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.
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
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000110148 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030898 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. S2CID 38395309.
- ^ "Entrez Gene: CCKBR cholecystokinin B receptor".
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- 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, 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. 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, Michejda CJ (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, Martinez J, Moroder L, Maigret B, Bouisson M, Vaysse N, Fourmy D (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, 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 (inactive 2024-03-26).
PMID
10741470.
{{ cite journal}}: CS1 maint: DOI inactive as of March 2024 ( link)
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.
PDB gallery | |
|---|---|
|
