Interaction of cholecystokinin with specific membrane receptors on pancreatic acinar cells

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Abstract
125I-labeled cholecystokinin [CCK] was prepared and the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas were examined. Binding of 125I-labeled CCK was reversible, temperature-dependent, saturable, specific and localized to the plasma membrane. Each acinar cell possessed approximately 9000 binding sites, and binding of the labeled peptide to these sites could be inhibited by cholecystokinin and structurally related peptides (e.g., gastrin and caerulein) as well as by nonpeptide competitive antagonists of the action of CCK. Binding was not inhibited by other pancreatic secretagogs such as secretin, vasoactive intestinal peptide, glucagon, physalaemin, eledoisin, kassinin, substance P, carbamoylcholine, litorin, or ranatensin or by bovine pancreatic polypeptide, atropine, neurotensin, Leu-enkephalin, Met-enkephalin or cyclic somatostatin. With agonists as well as antagonists, there was a good correlation between occupation of cholecystokinin binding sites and changes in acinar cell function. With each of 6 different peptide agonists maximal stimulation of enzyme secretion occurred with 40% receptor occupation and occupation of the remaining 60% caused a progressive decrease in stimulated amylase release. Agonists, but not antagonists, accelerated the dissociation of bound 125I-labeled cholecystokinin; in pancreatic acini, radiolabeled cholecystokinin may bind to at least 1 class of interacting binding sites whose affinities are influenced by the extent to which these sites are occupied by agonists, but not the extent to which they are occupied by antagonists.