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

Abstract

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 levels. In studies carried out in gastric gland microsomes, ethanol inhibited the hydrolytic activity of H+-K+-ATPase (EC50: 8.5 ± 0.6%), increased passive proton permeability (EC50: 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC50: 3%). Our results show that the inhibition of gastric acid secretion observed at low concentrations of ethanol (≤5%) is mainly caused by the specific impairment of H+-K+-ATPase-dependent proton transport across cell membranes rather than inhibition of the hydrolytic activity of H+-K+-ATPase, reduction in the cellular content of ATP, or increase in the passive permeability of membranes to protons, although these changes, in combination, must be relevant at concentrations of ethanol ≥7%.