M. Katz et al., EFFECT OF ETHANOL ON CHOLECYSTOKININ-STIMULATED ZYMOGEN CONVERSION INPANCREATIC ACINAR-CELLS, American journal of physiology: Gastrointestinal and liver physiology, 33(1), 1996, pp. 171-175
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.