Impairment of H+-K+-ATPase-dependent proton transport and inhibition of gastric acid secretion by ethanol

Ethanol (1-20% vol/vol) caused a dose-dependent reduction in the basal rate of acid formation in isolated rabbit gastric glands with a calculated EC50 value of 4.5 +/- 0.2%. Ethanol also reduced ATP levels in isolated gastric glands and in cultured parietal cells (EC50 : 8.8 +/- 0.4% and 8.5 +/- 0.2 %, respectively) and decreased both basal and forskolin-stimulated cAMP lev els. In studies carried out in gastric gland microsomes, ethanol inhibited the hydrolytic activity of H+-K+-ATPase (EC50 : 8.5 +/- 0.6%), increased pa ssive proton permeability (EC50 : 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC50 : 3%). Our results show that the inhibition of gast ric acid secretion observed at low concentrations of ethanol (less than or equal to5%) is mainly caused by the specific impairment of H+-K+-ATPase- de pendent proton transport across cell membranes rather than inhibition of th e hydrolytic activity of H+-K+-ATPase, reduction in the cellular content of ATP, or increase in the passive permeability of membranes to protons, alth ough these changes, in combination, must be relevant at concentrations of e thanol greater than or equal to7%.