Enhanced Intracellular Calcium Promotes Metabolic and Secretory Disturbances in Rat Gastric Mucosa during Ethanol-Induced Gastritis

Abstract

Changes in the Ca2+ homeostasis have been implicated in cell injury and death. However, Ca2+ participation in ethanol-induced chronic gastric mucosal injury has not been elucidated. We have developed a model of ethanol-induced chronic gastric injury in rats, characterized by marked alterations in plasma membranes from gastric mucosa and a compensatory cell proliferation, which follows ethanol withdrawal. Therefore, the present study explored the possible role of intracellular Ca2+ in the oxidative metabolism and in acid secretion in this experimental model. Glucose oxidation was greatly enhanced in the injured mucosa, as evaluated by CO2 production by isolated mucosal preparations incubated with 14C-radiolabeled glucose in different carbons. Oxygen consumption and acid secretion (aminopyrine accumulation) were also stimulated. A predominating secretory status was morphologically identified by electron microscopy in oxyntic cells of gastric mucosa from ethanol-treated rats. A coupling between secretory and metabolic effects induced by ethanol (demonstrated by an inhibitory effect of omeprazole in both parameters) was found. These ethanol-induced effects were also inhibited by addition of Ca2+ chelators to isolated gastric mucosa samples. Lanthanum, a Ca2+ channel blocker, inhibited ethanol-promoted increase of oxidative metabolism. In addition, a stimulated Ca2+ uptake by mucosal minces and increased in vivo Ca2+ levels in cytosolic and mitochondrial fractions, were also noticed. Enhanced glucose and oxygen consumptions were associated with higher ATP and NADP+ availability, whereas cytosolic NAD/NADH ratio (assessed by mucosal levels of lactate and pyruvate) was not significantly modified by the chronic ethanol administration. In conclusion, changes in Ca2+ homeostasis, probably mainly due to increased extracellular Ca2+ uptake, could mediate secretory and metabolic alterations found in the gastric mucosa from rats chronically treated with ethanol.