Overview: Cholecystokinin receptors (nomenclature recommended by the NC-IUPHAR Subcommittee on CCK receptors, Noble et al., 1999) are activated by the endogenous peptides cholecystokinin (CCK)-4, CCK-8, CCK-33 and gastrin. There is evidence for species homologues of CCK2 receptors distinguished by the relative affinities of the two stereoisomers of devazepide, R-L365260 and S-L365260, or by the differences in affinity of the agonist BC264 (Durieux et al., 1992).
| Nomenclature | CCK1 | CCK2 |
|---|---|---|
| Other names | CCKA | CCKB, CCKB/gastrin |
| Ensembl ID | ENSG00000163394 | ENSG00000110148 |
| Principal transduction | Gq/11/Gs | Gs |
| Rank order of potency | CCK-8 >> gastrin, des-CCK-8 > CCK-4 | CCK-8 ≥ gastrin, des-CCK-8, CCK-4 |
| Selective agonists | A71623, JMV180, GW5823 | Desulfated CCK-8, gastrin, CCK-4, BC264, RB400 |
| Selective antagonists | Devazepide (9.8), T0632 (9.6), SR27897 (9.2), IQM95333 (9.2), PD140548 (7.9–8.6), lorglumide (7.2) | YM022 (10.2), L740093 (10.0), GV150013 (9.3), RP73870 (9.3), L365260 (7.5–8.7), LY262691 (7.5) |
| Probes | [3H]-Devazepide (0.2 nM) | [3H]-Propionyl-BC264 (0.15 nM), [3H]-PD140376 (0.2 nM), [3H]-L365260 (2 nM), [3H]- or [125I]-gastrin (1 nM), [125I]-PD142308 (0.25 nM) |
A mitogenic gastrin receptor, which can be radiolabelled with [125I]-gastrin-(1–17) and which appears to couple to the Gs family of G proteins, has been described in human colon cancer cells (Bold et al., 1994) and other cell lines (e.g. pancreatic AR42J and Swiss 3T3 fibroblasts, Seva et al., 1994; Singh et al., 1995).
Glossary
Abbreviations:
- A71623
Boc-Trp-Lys(O-toluylaminocarbonyl)-Asp-(NMe)Phe-NH2
- BC264
Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2
- GV150013
(+)-N-(1-[1-adamantane-1-methyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl)-N'-phenylurea
- GW5823
2-[3-(1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(methyoxyphenyl)acetamide
- IQM95333
(4αS,5R)-2-benzyl-5[N-(tert-butoxycarbonyl)-L-Trp]amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine
- JMV180
Boc-Tyr(SO3H)Ahx-Gly-Trp-Ahx-Asp2phenylethyl ester
- L365260
3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N'-(3-methylphenyl)urea
- L740093
N-([3R]-5-[3-azabicyclo{3.2.2}nonan-3-yl]-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl)-N'-(3-methylphenyl)urea
- LY262691
trans-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-pyrrazolidinecarboxamide(3.3.1.13,7)
- PD140376
L-3-([4-aminophenyl]methyl)-N-(α-methyl-N-[{tricyclo(3.3.1.1D-Trp)-β-Ala
- PD140548
N-(α-methyl-N-[{tricyclo(3.3.1.1L-Trp)-D-3-(phenylmethyl)-β-Ala
- PD142308
iodinated PD140548
- RB400
HOOC-CH2-CO-Trp-NMe(Nle)-Asp-Phe-NH2
- RP73870
({[(RS)
- SR27897
1-([2-{4-(2-chlorophenyl)thiazole-2-yl}aminocarbonyl]indolyl)acetic acid
- T0632
sodium (S)-3-(1-[2-fluorophenyl]-2,3-dihydro-3-[{3-isoquinolinyl}-carbonyl]amino-6-methoxy-2-oxo-1H-indole)propanoate
- YM022
(R)-1-(2,3-dihydro-1-[2'-methylphenacyl]-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-3-(3-methylphenyl)urea
Further Reading
Berna MJ, Tapia JA, Sancho V, Jensen RT (2007). Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have a therapeutic potential. Curr Opin Pharmacol7: 583–592.
De Tullio P, Delarge J, Pirotte B (2000). Therapeutic and chemical developments of cholecystokinin receptor ligands. Expert Opin Investig Drugs9: 129–146.
Dockray GK (2009). Cholecystokinin and gut-brain signalling. Regul Pept155: 6–10.
Dufresne M, Seva C, Fourmy D (2006). Cholecystokinin and gastrin receptors. Physiol Rev86: 805–847.
Herranz R (2003). Cholecystokinin antagonists: pharmacological and therapeutic potential. Med Res Rev23: 559–605.
Inui A (2003). Neuropeptide gene polymorphisms and human behavioural disorders. Nat Rev Drug Discov2: 986–998.
Kopin AS, McBride EW, Schaffer K, Beinboen M (2000). CCK receptor polymorphisms: an illustration of emerging themes in pharmacogenomics. Trends Pharmacol Sci21: 346–353.
Miller LJ, Gao F (2008). Structural basis of cholecystokinin receptor binding and regulation. Pharmacol Ther119: 83–95.
Moran TH (2000). Cholecystokinin and satiety: current perspectives. Nutrition16: 858–865.
Noble F, Roques BP (1999). CCKB receptor: chemistry, molecular biology, biochemistry and pharmacology. Prog Neurobiol56: 1–31.
Noble F, Wank SA, Crawley JN, Bradwejn J, Seroogy KB, Hamon M et al. (1999). International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev51: 745–781.
Peter SA, D’Amato M, Beglinger C (2006). CCKI antagonists: are they ready for clinical use? Dig Dis24: 70–82.
Raybould HE (2007). Mechanismsm of CCK signaling from gut to brain. Curr Opin Pharmacol7: 570–574.
Rozengurt E, Walsh J (2001). Gastrin, CCK, signaling, and cancer. Annu Rev Physiol63: 49–76.
References
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