Cholecystokinin B receptor

The cholecystokinin B receptor also known as CCKBR or CCK2 is a is_associated_with::protein that in humans is encoded by the CCKBR is_associated_with::gene.

This gene encodes a is_associated_with::G protein-coupled receptor for is_associated_with::gastrin and is_associated_with::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
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 is_associated_with::dopamine activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing the is_associated_with::dopamine-enhancing effects of CCK-A. However, the effects of CCK-B on is_associated_with::dopamine activity vary depending on location. CCK-B antagonism enhances dopamine release in rat striatum. Activation enhances is_associated_with::GABA release in rat anterior is_associated_with::nucleus accumbens. CCK-B receptors modulate dopamine release, and influence the development of tolerance to is_associated_with::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 is_associated_with::cocaine-induced is_associated_with::conditioned place preference, and prevents the long-term maintenance and reinstatement of is_associated_with::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 is_associated_with::squirrel monkeys induces significant enhancement of locomotor response to is_associated_with::L-DOPA. 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.

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

 * is_associated_with::Cholecystokinin
 * is_associated_with::CCK-4
 * is_associated_with::Gastrin
 * BBL-454

Antagonists

 * is_associated_with::Proglumide
 * is_associated_with::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