Calcium-dependent signaling of acid secretion in isolated parietal cells from guinea pigs and its modification by ethanol

Treatment of isolated parietal cells from guinea pig gastric mucosa with ethanol caused a rapid increase in [Ca2+]i and concomitant decrease in the capacity for carbachol-stimulated acid secretion in a dose dependent manner. Carbachol rapidly increased the [Ca2+]i from trimethoxybenzoic acid 8-(diethylamino)-octyl ester sensitive intracellular pool. In contrast, the increase with ethanol was through La3+ sensitive Ca2+ channel from external source, which suppressed the Ca2+ response subsequently stimulated with carbachol. Pretreatment of the cells with EGTA or La3+ completely prevented the elevation of [Ca2+]i with ethanol and preserved the Ca2+ response to carbachol. These findings indicate that ethanol-induced elevation of [Ca2+]i may desensitize the stimulation of carbachol. Furthermore, treatment of the parietal cells with ethanol increased the activity of protein kinase C in both cytosolic and membrane fractions of the cells. Activation of protein kinase C with phorbol diester suppressed the capacity for acid secretion. These results suggest that ethanol may inhibit the carbachol-stimulated acid secretion through the desensitization of Ca2+ response and the activation of protein kinase C.