The integrity of the cholecystokinin receptor gene in gallbladder disease and obesity

✍ Scribed by Gerardo Nardone; Irene A. Ferber; Laurence J. Miller

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 372 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220621

✦ Synopsis

Cholesterol gallstone disease and obesity are common and often associated disorders that could be affected by dysfunction of the receptor for cholecystokinin (CCK). Extending earlier studies that identified a defect at the level of receptor-G protein coupling in cholesterol gallstone disease, we characterized the primary structure of the gallbladder CCK receptor in patients undergoing a cholecystectomy. Represented were patients with cholesterol gallstones, as well as controls with pigment gallstones or without gallbladder disease. Both groups were composed of the range of body habitus from lean to morbidly obese. No evidence of any sequence mutation or polymorphism in the CCK receptor gene was found in any patient. This should lead future investigations of the pathogenesis of these problems toward the possible contribution of the plasmalemmal environment in affecting the association between normal receptors and G proteins. (J~EPATOLOGY 1995;22:1751-1753.) Receptors for peptide hormones are situated in the plasma membrane of target cells at the interface between the exquisitely low concentrations of circulating hormone and the intracellular activity cascades mediating cellular effects of those messengers. Because of this, receptors represent a key step in cellular regulation when the hormone-stimulated signal is transduced across the lipid bilayer. Recently it has been shown that receptor mutations may occur naturally and may represent the molecular basis for cellular dysfunction in disease states.' Powerful methods of molecular biology study make it possible to recognize and identify such mutations, as well as polymorphisms that may be present.

Cholecystokinin (CCK) is a peptide hormone that initiates its activity by binding to a guanine nucleotidebinding protein (G protein)-coupled receptor in the p-Abbreviations: CCK, cholecystokinin; cDNA, complementary DNA, PCR, From the Center for Basic Research in Digestive Diseases, Mayo Clinic and