Cholecystokinin B receptor
Encyclopedia
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein
that in humans is encoded by the CCKBR gene
.
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.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the CCKBR gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
This gene encodes a G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
for gastrin
Gastrin
In humans, gastrin is a peptide hormone that stimulates secretion of gastric acid by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the antrum of the stomach, duodenum, and the pancreas...
and cholecystokinin
Cholecystokinin
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
(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
CCKCholecystokinin
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing the dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
-enhancing effects of CCK-A
Cholecystokinin A receptor
The extracellular, N-terminal, domain of this protein adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop...
. However, the effects of CCK-B on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
activity vary depending on location. CCK-B antagonism enhances dopamine release in rat striatum. Activation enhances GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
release in rat anterior nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
. 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
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
-induced conditioned place preference
Conditioned place preference
Conditioned place preference is a technique commonly used in animal studies to evaluate preferences for environmental stimuli that have been associated with a positive or negative reward...
, and prevents the long-term maintenance and reinstatement of morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
-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
The cholecystokinin B receptor is stimulated by CCK and Gastrin in the stomach during digestion.Antagonists
- ProglumideProglumideProglumide is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes...
- CI-988CI-988CI-988 is a drug which acts as a cholecystokinin antagonist, selective for the CCKB subtype. In animal studies it showed anxiolytic effects and potentiated the analgesic action of both morphine and endogenous opioid peptides, as well as preventing the development of tolerance to opioids and...
- CI-1015
- L-365,260
- L-369,293
- YF-476
- YM-022
- RP-69758
- LY-225,910
- LY-288,513
- PD-135,158
- PD-145,942