Effects of prostaglandin E2 on salicylate-induced damage to the rat gastric mucosa: cytoprotection is not associated with preservation of the gastric mucosal barrier

Abstract

The effects of pretreatment with prostaglandin E2 (PGE2) on salicylate-induced gastric damage in the rat were studied with a gastric chamber model. Transmural potential difference (PD) and net K+ efflux were monitored as indices of gastric mucosal barrier integrity. Topical application of 20 mM salicylate for 10 min produced an abrupt drop in PD, an increase in net K+ flux, and the formation of hemorrhage erosions covering .apprx. 24% of the glandular mucosa. Prior topical application of PGE2 at doses of 25, 75 and 300 .mu.g/kg significantly reduced the extent of hemorrhagic erosions. PG pretreatment did not produce a reduction in the effects of topical salicylate on either PD or net K+ efflux. The drop in PD was initially accelerated, and the net K+ efflux was increased, by PGE2 pretreatment. Subsequently, in PGE2-pretreated mucosae, both parameters showed more rapid recovery toward control values. The mechanism of cytoprotection by PGE2 against salicylate-induced gastric damage apparently is not a consequence of preservation of the gastric mucosal barrier.