Alteration in gastric mucosal acid protease activity induced by necrotizing agents and prevention by prostaglandin E2

Tissue levels of two gastric mucosal acid proteases, pepsinogen and cathepsin D-like acid proteinase, were determined in rat gastric mucosa damaged by various necrotizing agents and the protective effects of prostaglandins against these biological alterations were investigated. Gastric mucosal damage by each necrotizing agent used was associated with a marked decrease in tissue level of cathepsin D-like acid proteinase. Particularly, ethanol ingestion caused its significant reduction parallel to the production of gastric lesions in a time-dependent manner. On the other hand, mucosal pepsinogen level increased markedly only in ethanol-damaged gastric mucosa, indicating that this change was mediated by a different mechanism from that for cathepsin D-like enzyme. In rats pretreated with prostaglandin E2 and prostaglandin inducers before ethanol administration, these biological alterations of two enzymes were effectively prevented as were gastric lesions. However, ethanol ingestion caused these changes to occur to the same degree in both the necrotic and non-necrotic areas of glandular mucosa. It was considered that cathepsin D-like acid proteinase was released from damaged gastric mucosa through a direct action on cellular membrane different from vasoconstrictor and platelet aggregating actions mediated by arachidonic acid metabolites.