Cholecystokinin B receptor

The cholecystokinin B receptor also known as CCKBR or CCK₂ is a protein^[5] that in humans is encoded by the CCKBR gene.^[6]

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
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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