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 EC(50) value of 4.5 +/- 0.2%. Ethanol also reduced ATP levels in isolated gastric glands and in cultured parietal cells (EC(50): 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(EC(50): 8.5 +/- 0.6%), increased passive proton permeability (EC(50): 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC(50): 3%). Our results show that the inhibition of gastric acid secretion observed at low concentrations of ethanol (< or =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 > or =7%.

Ethanol Inhibits Gastric Acid Secretion in Rats Through Increased AMP-Kinase Activity

“…As a consequence, numerous attempts have been made in the past to study its effects on the ability of the stomach to produce acid [9][10][11][12]. However, the results of these studies were very ambiguous in that no consensus has been reached as to whether ethanol inhibits or stimulates gastric acid secretion [9][10][11][12].…”

“…As a consequence, numerous attempts have been made in the past to study its effects on the ability of the stomach to produce acid [9][10][11][12]. However, the results of these studies were very ambiguous in that no consensus has been reached as to whether ethanol inhibits or stimulates gastric acid secretion [9][10][11][12]. Beside the observation that there might be a biphasic effect of ethanol distinguishing between acute and chronic exposure [31,32], the fact that many groups have employed remarkably high doses of ethanol (with up to 20% being classified as low-dose exposure) and different experimental approaches, ranging from studies in cultured cells to observations on the wholetissue level, may account for the heterogeneous past results [9][10][11][12].…”

“…There has been a great deal of controversy as to the effects of ethanol on gastric acid secretion from being a mild stimulant to being a potent inhibitor [9][10][11][12]. However, the general consensus implicated that alcoholic beverages stimulate gastric acid secretion.…”

“…In sharp contrast to these findings, other investigations concluded that acid secretion is reduced under low-dose conditions. Del Valle et al not only demonstrated cessation of acid secretion following low-dose (1-20%) ethanol exposure, but also decreased ATP and cAMP concentrations in the affected parietal cells [10]. Niki et al observed similar inhibition of carbachol-and histamine-triggered proton extrusion [11].…”

Loss of parietal cell superoxide dismutase leads to gastric oxidative stress and increased injury susceptibility in mice

“…ATP depletion is a prominent feature underlying necrosis (51), so it is reasonable to infer that a compromised metabolic state would adversely impact the susceptibility to gastric mucosal injury. Moreover, ATP depletion and reduced mitochondrial ATP synthase expression have been implicated in gastric mucosal injury induced by exposure to concentrated alcohol (7,39). By contrast, gastric mucosal restitution following injury appears to rely predominantly on glycolysis (5).…”