Effects of Proglumide on Pancreatic Acinar Cell Function

Abstract

Proglumide, a putative gastrin receptor antagonist, inhibited cholecystokinin (CCK)-stimulated amylase release and [³H]-2-deoxy-D-glucose uptake by isolated mouse pancreatic acini. Inhibition was reversible and competitive in nature with a K_Iof 0.7 mM. Proglumide also competitively inhibited the binding of ¹²⁵I-CCK to its receptor in pancreas and brain; the K_I for this interaction was 1.0 mM. In contrast, proglumide did not inhibit carbachol-stimulated amylase release, insulin-stimulated glucose transport and protein synthesis, or the binding of insulin to its receptors. Proglumide at 10 mM did, however, reduce both basal [³H]-2-deoxy-D-glucose uptake and [³H]-leucine incorporation into protein. We conclude that proglumide is a competitive and specific, albeit weak antagonist of CCK receptors. Higher concentrations of the drug may have other more nonspecific effects.