EFFECT OF ETHANOL ON CHOLECYSTOKININ-STIMULATED ZYMOGEN CONVERSION INPANCREATIC ACINAR-CELLS

Exocrine pancreatic zymogens are proteolytically processed to active f orms after they are secreted into the small intestine. However, intrac ellular conversion of zymogens to active forms can be stimulated by tr eating pancreatic acinar cells with high doses of cholecystokinin (0.1 mu M) or carbamylcholine (0.1 mM). The high doses of cholecystokinin are unlikely to be achieved physiologically. The ability of ethanol to sensitize the acinar cell to zymogen conversion induced by cholecysto kinin or carbamylcholine was examined. Ethanol (10-200 mM) had no effe ct alone or when combined with carbamylcholine. However, ethanol (25 m M) added with low-dose cholecystokinin (0.1 nM) generated zymogen conv ersion that was 1) sixfold higher than cholecystokinin alone and 2) eq uivalent to that generated by high-dose cholecystokinin (10 mu M). The ability of ethanol to enhance cholecystokinin-induced zymogen convers ion was dependent on the dose of ethanol and the duration of ethanol t reatment. The cholecystokinin receptor antagonist, L-364,718, blocked the conversion stimulated by the addition of ethanol with cholecystoki nin. This effect of ethanol did not change the affinity or number of c holecystokinin receptors, suggesting an effect more distal in the stim ulus-activation cascade. These findings demonstrate that ethanol selec tively sensitizes the pancreatic acinar cell to cholecystokinin-stimul ated zymogen proteolysis.