Biology:Cholecystokinin B receptor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein[1] that in humans is encoded by the CCKBR gene.[2]

This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin (CCK),[3][4][5] 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.[6]

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.[7] CCK-B antagonism enhances dopamine release in rat striatum.[8] Activation enhances GABA release in rat anterior nucleus accumbens.[9] CCK-B receptors modulate dopamine release, and influence the development of tolerance to opioids.[10] CCK-B activation decreases amphetamine-induced DA release, and contributes to individual variability in response to amphetamine.[11]

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.[12] Blockade of CCK-B potentiates cocaine-induced dopamine overflow in rat striatum.[8] 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.[13] 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.[14]

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

See also

References

  1. ↑ "CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology". Progress in Neurobiology 58 (4): 349–79. Jul 1999. doi:10.1016/S0301-0082(98)00090-2. PMID 10368033. 
  2. ↑ "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. Nov 1992. doi:10.1016/0006-291X(92)91557-7. PMID 1280419. PMC 6719700. https://zenodo.org/record/1253810. 
  3. ↑ "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. Jan 2005. doi:10.1074/jbc.M409480200. PMID 15520004. 
  4. ↑ "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". Journal of Nuclear Medicine 45 (3): 485–94. Mar 2004. PMID 15001692. 
  5. ↑ "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. May 2003. doi:10.1124/mol.63.5.973. PMID 12695525. 
  6. ↑ "Entrez Gene: CCKBR cholecystokinin B receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=887. 
  7. ↑ "Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin". Brain Research 483 (2): 321–6. Apr 1989. doi:10.1016/0006-8993(89)90176-5. PMID 2706523. 
  8. ↑ 8.0 8.1 "Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum". Life Sciences 73 (6): 727–39. Jun 2003. doi:10.1016/S0024-3205(03)00393-X. PMID 12801594. 
  9. ↑ "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. Jan 2000. doi:10.1007/s002109900161. PMID 10651144. 
  10. ↑ "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. Jan 1990. doi:10.1016/0014-2999(90)90129-T. PMID 2311658. 
  11. ↑ "Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion". Pharmacology Biochemistry and Behavior 48 (4): 1019–24. Aug 1994. doi:10.1016/0091-3057(94)90214-3. PMID 7972279. 
  12. ↑ "Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats". Behavioural Brain Research 120 (1): 105–10. Apr 2001. doi:10.1016/S0166-4328(00)00361-2. PMID 11173090. 
  13. ↑ "Modulatory role for CCK-B antagonists in Parkinson's disease". Clinical Neuropharmacology 13 (4): 339–47. Aug 1990. doi:10.1097/00002826-199008000-00009. PMID 1976438. 
  14. ↑ "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease". Pharmacogenetics 13 (6): 365–9. Jun 2003. doi:10.1097/00008571-200306000-00008. PMID 12777967. 

Further reading

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.



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