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Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
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.
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. 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.
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.
- ↑ Noble F, Roques BP (July 1999). CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology. Prog. Neurobiol. 58 (4): 349–79.
- ↑ Pisegna JR, de Weerth A, Huppi K, Wank SA (November 1992). Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. Biochem. Biophys. Res. Commun. 189 (1): 296–303.
- ↑ Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (January 2005). Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy. J. Biol. Chem. 280 (2): 1044–50.
- ↑ Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (March 2004). In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging. J. Nucl. Med. 45 (3): 485–94.
- ↑ 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. Mol. Pharmacol. 63 (5): 973–82.
- ↑ Entrez Gene: CCKBR cholecystokinin B receptor.
- ↑ Altar CA, Boyar WC (April 1989). Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin. Brain Res. 483 (2): 321–6.
- ↑ 8.0 8.1 Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (June 2003). Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum. Life Sci. 73 (6): 727–39.
- ↑ Lanza M, Makovec F (January 2000). Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons. Naunyn Schmiedebergs Arch. Pharmacol. 361 (1): 33–8.
- ↑ Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (January 1990). The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur. J. Pharmacol. 176 (1): 35–44.
- ↑ Higgins GA, Sills TL, Tomkins DM, Sellers EM, Vaccarino FJ (August 1994). Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion. Pharmacol. Biochem. Behav. 48 (4): 1019–24.
- ↑ Lu L, Huang M, Ma L, Li J (April 2001). Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats. Behav. Brain Res. 120 (1): 105–10.
- ↑ Boyce S, Rupniak NM, Tye S, Steventon MJ, Iversen SD (August 1990). Modulatory role for CCK-B antagonists in Parkinson's disease. Clin Neuropharmacol 13 (4): 339–47.
- Herget T (1994). Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors. Ann. N. Y. Acad. Sci. 713: 283–97.
- Lee YM (1993). The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J. Biol. Chem. 268 (11): 8164–9.
- Ito M (1995). Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ. 5 (10): 1127–35.
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- de Weerth A, Pisegna JR, Huppi K, Wank SA (1993). Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor. Biochem. Biophys. Res. Commun. 194 (2): 811–8.
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- Beinborn M (1993). A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists. Nature 362 (6418): 348–50.
- Silvente-Poirot S, Wank SA (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. J. Biol. Chem. 271 (25): 14698–706.
- Tarasova NI (1997). Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor. Cell Tissue Res. 287 (2): 325–33.
- Suzuki Y (1997). Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. Gene 200 (1–2): 149–56.
- O'Briant KC, Ali SY, Weier HU, Bepler G (1999). 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 Res. 6 (5): 415–8.
- Monstein HJ, Nilsson I, Ellnebo-Svedlund K, Svensson SP (1999). Cloning and characterization of 5'-end alternatively spliced human cholecystokinin-B receptor mRNAs. Recept. Channels 6 (3): 165–77.
- Daulhac L (1999). Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors. J. Biol. Chem. 274 (29): 20657–63.
- Silvente-Poirot S (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. J. Biol. Chem. 274 (33): 23191–7.
- Kulaksiz H (2000). Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach. Cell Tissue Res. 299 (2): 289–98.
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