Effect of ethanol on cholecystokinin-induced enzyme secretion from isolated rat pancreatic acini

Cholecystokinin octapeptide (CCK 8 )-stimulated amylase release in isolated rat pancreatic acini was inhibited over 30% by 600 mM ethanol. The configuration of the dose-response curve for CCK 8 , however, in the presence of ethanol was similar to that of the control. Amylase release elicited by maximal concentrations of CCK 8 (300 pM) was inhibited by increasing concentrations of ethanol (0.3 to 1.3 M), and this inhibition was concentration dependent. In addition, the binding of [ 125 I]CCK 33 to specific membrane receptors on acini was inhibited by ethanol in a dose-dependent manner. A positive correlation between the inhibitory effects of ethanol on CCK binding and CCK-induced amylase release was observed. Furthermore, these inhibitory effects of ethanol were reversible. Basal amylase release, however, was increased 20–50% by ethanol between the concentrations of 0.3 and 1.3M; higher concentrations caused a leakage of amylase from the acini both in the absence and presence of 300 pMCCK 8 . This is confirmed by 51 Cr release from prelabeled acini which revealed no significant damage to acinar cell membrane between 0.3 and 1.6 M ethanol, but significant damage to acini at higher concentrations. These data suggest that the 600 mM ethanol-induced inhibition of CCK action in acini is due to reversible perturbation of the acinar cell membrane.