Role of locally generated prostaglandins in adaptive gastric cytoprotection

This study was designed to determine the role of mucosal generation of prostaglandins (PGs) in the ability of mild irritants (20% ethanol or 5% NaCl) to protect against the formation of mucosal lesions caused by necrotizing agents (100% ethanol or 25% NaCl) or acidified aspirin (ASA). Mild irritants protected damage from necrotizing agents but not from ASA. This protection was accompanied by increased mucosal generation of PGE2 and PGI2-like substances. Exogenous PGE2 and PGI2 applied topically to the gastric mucosa in a nonantisecretory dose greatly inhibited the formation of lesions induced by either necrotizing agents or ASA. Pretreatment with indomethacin, which suppressed the generation of mucosal PGs augmented formation of lesions by necrotizing agents and partly counteracted the protective effect of mild irritants. We conclude that mild irritants, and exogenous PGs inhibit the formation of gastric lesions by necrotizing agents, at least in part, by mucosal generation of PGs.