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)
End	6,272,127 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	105,120,105 bp
RNA expression pattern
	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
	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
	887
	12426
	ENSG00000110148
	ENSMUSG00000030898
	P32239
	P56481
	NM_176875; NM_001318029; NM_001363552
	NM_007627
	NP_001304958; NP_795344; NP_001350481
	NP_031653
	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.

Selective Ligands

The cholecystokinin B receptor responds to a number of ligands.

Agonists

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

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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000110148 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid10368033-5] 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.

[pmid1280419-6] 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.

[pmid15520004-7] 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.

[pmid15001692-8] 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.

[pmid12695525-9] 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-10] "Entrez Gene: CCKBR cholecystokinin B receptor".

[pmid2706523-11] 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.

[Loonam_2003-12] 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.

[pmid10651144-13] 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.

[pmid2311658-14] 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.

[pmid7972279-15] 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.

[pmid11173090-16] 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.

[pmid1976438-17] 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.

[pmid12777967-18] 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.

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