The cholecystokinin B receptor also known as CCKBR or CCK
2 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''CCKBR''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This gene encodes a
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...
for
gastrin
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
...
and
cholecystokinin
Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat a ...
(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
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
activity in the brain. CCK-B activation appears to possess a general inhibitory action on dopamine activity in the brain, opposing the
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
-enhancing effects of
CCK-A. However, the effects of CCK-B on
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
activity vary depending on location.
CCK-B antagonism enhances dopamine release in rat striatum.
Activation enhances
GABA
GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
GA ...
release in rat anterior
nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
.
CCK-B receptors modulate dopamine release, and influence the development of tolerance to
opioid
Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s.
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 is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
-induced
conditioned place preference, and prevents the long-term maintenance and reinstatement of
morphine
Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...
-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
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
. Blockade of CCK-B in dopamine-depleted
squirrel monkeys
Squirrel monkeys are New World monkeys of the genus ''Saimiri''. ''Saimiri'' is the only genus in the subfamily Saimiriinae. The name of the genus is of Tupi origin (''sai-mirím'' or ''çai-mbirín'', with ''sai'' meaning 'monkey' and ''mirím' ...
induces significant enhancement of
locomotor response to
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
*
Cholecystokinin
Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat a ...
*
CCK-4
Cholecystokinin tetrapeptide (CCK-4, tetragastrin, Trp- Met- Asp- Phe-NH2) is a peptide fragment derived from the larger peptide hormone cholecystokinin. Unlike cholecystokin which has a variety of roles in the gastrointestinal system as well ...
*
Gastrin
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
...
* BBL-454
Antagonists
*
Proglumide
Proglumide, sold under the brand name Milid, is a drug that inhibits gastrointestinal motility
Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at v ...
*
CI-988
CI-988 (PD-134,308) 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
Morphine, formerly also cal ...
* 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 receptors or CCK receptors are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) and gastrin. There are two different subtypes CCKA and CCKB which are ~50% homologous: Various chole ...
*
Cholecystokinin antagonist
A cholecystokinin receptor antagonist is a specific type of receptor antagonist which blocks the receptor sites for the peptide hormone cholecystokinin (CCK).
Classification
There are two subtypes of this receptor known at present, defined as ...
References
Further reading
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External links
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{{Neuropeptide receptors
G protein-coupled receptors
Cholecystokinin receptors