Role of CCK in Gallbladder Function

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Abstract
Cholecystokinin may play a role in regulation of interdigestive motility, but this still remains to be investigated. CCK constitutes the major hormonal stimulus for postprandial gallbladder emptying. CCK exerts its contractile effects mainly through interaction directly with receptors on the gallbladder smooth muscle cells in the muscle layer, but also through interaction with cholinergic nerves extrinsic and/or intrinsic in nature. Furthermore, CCK can enhance ongoing nicotinic ganglionic transmission occurring in the serosal layer by release of acetylcholine. CCK interaction with the gallbladder smooth muscle CCKA receptor was studied in further detail. CCK contracts strips of gallbladder muscle in a concentration-dependent way with a potency in the nanomolar range in all tested species. The potency is 1,000-fold better than that of gastrin; thus, the receptor is of type CCKA. CCK binding to this receptor is specific and of high affinity, 1,000-fold better than that of gastrin with no differences between the tested species including bovine, porcine, and human. Also, CCK binding affinity was independent of age, gender, or weight of the person and pathology of the human gallbladder. The biochemistry of the CCKA receptor varies between the tested species (bovine and human). Both CCKA receptors are heavily glycosylated, but of different size and carbohydrate content. The bovine CCKA receptor is of apparent size M(r) = 70-85 kD with N-linked complex carbohydrates and sialic acids. The human CCKA receptor is of M(r) = 85-95 kD, with N-linked complex carbohydrates, but no sialic acids. They both have a protein core of apparent size M(r) = 43 kD, with almost identically sized fragments after enzymatic cleavage. Probably the protein cores contain the receptor binding region, which seems well preserved between species. CCK and the CCKA gallbladder muscularis receptor are main regulators of postprandial gallbladder emptying. The biochemistry of the CCKA gallbladder smooth muscle receptor is in accord with newly generated data of purification and cloning of the rat pancreatic CCKA receptor.