Ethanol, its effect on the synthesis of proteins by guinea-pig gastric mucosa

Incorporation of L-[U-14C]leucine into proteins is taken to indicate the synthesis of proteins by guinea pig gastric mucosa. Ethanol reduced the synthesis of proteins in vitro by homogenized mucosa, by isolated gastric epithelial cell preparations and by intact tissue. Intact stomach wall incubated without ethanol in phosphate buffered saline showed progressively increasing incorporation of the precursor into tissue proteins and into proteins which were secreted into the mucosal incubation media. On isopycnic CsCl gradient fractionation radioactive tissue proteins were found at the top of the gradient (fraction L1, sp.gr.1.11-1.20) while radioactive secreted proteins sedimented to the bottom of the gradient as the carbohydrate rich high density gastric mucosal glycoprotein fraction L3 (sp.gr.1.29-1.33). Ethanol significantly but reversibly reduced the incorporation of radioactive leucine by intact mucosa into both the tissue proteins and the secreted proteins. Uptake of the precursor into the intracellular acid soluble pool was not impaired by ethanol and no significant differences were detected in the specific activities of free intracellular leucine between the ethanol treated samples and the corresponding controls. It is suggested that the ulcerogenic nature of ethanol may be associated with inhibition of the synthesis of proteins within mucosal epithelium leading to reduction in the output of mucosal secretory glycoproteins with subsequent impairment of the cytoprotective properties of the dynamic mucous barrier.