| [ Summary ] |
Two types of cholecystokinin(CCK) receptors(type A and type B), which are seven transmembrane G-protein coupled receptors, have been identified on the basis of their affinities for a structurally and functionally related family of peptides, with identical COOH-terminal pentapeptide sequences. These receptors were cloned, and a CCK-B receptor(CCK-BR) gene was found to be identical to the gastrin receptor gene. We demonstrated the absence of the CCK-AR gene expression due to a genetic abnormality in OLETF rats, which show a tendency toward obesity and non-insulin dependent diabetes mellitus, although the expression of the CCK-BR gene was intact. This rat is a naturally occurring CCK-AR knockout rat, and a useful tool for evaluating CCK-AR functions. CCK stimulates pancreatic enzyme secretion and produces gall-bladder contraction, through CCK-AR. In the human pancreas CCK-BR mRNA was expressed, but not CCK-AR, indicating an indirect effect on exocrine pancreatic functioning. The polymorphism in the promoter region of the CCK-AR gene may be a genetic factor, affecting obesity and abnormalities in gallbladder contraction. |