Effects of proglumide on ductal and basolateral secretion of pancreatic digestive enzymes

Previous studies have shown that proglumide acts as a cholecystokinin (CCK) receptor antagonist in isolated pancreatic acini. To establish the effect of proglumide in the intact organ, its effects on both CCK-stimulated ductal and basolateral secretion of digestive enzymes were studied in the in vitro rabbit pancreas. CCK-stimulated ductal secretion of chymotrypsinogen, amylase, and total protein, as well as basolateral secretion of amylase, was inhibited by proglumide in a dose-dependent manner. Regression lines comparing ductal chymotrypsinogen and amylase outputs also were altered significantly by proglumide in a dose-dependent manner, with amylase secretion inhibited to a lesser degree. Similarly, the relative rates of amylase secretion across the ductal versus the basolateral cell surface were altered, with basolateral secretion inhibited to a lesser degree. The effects seen with increasing concentrations of proglumide at a given concentration of CCK mirrored the effects seen with decreasing the concentration of CCK in the absence of proglumide. Proglumide did not affect ductal or basolateral secretion stimulated by a cholinergic agonist and did not affect unstimulated pancreatic secretion. Thus, proglumide appears to act as a selective antagonist of CCK-stimulated secretion in the intact organ. The results further indicate that interactions of an agonist and an antagonist at the CCK receptor can alter not only the overall amount of enzymes secreted but their relative proportions as well.