Effects of prostaglandin E2 on salicylate-induced damage to the rat gastric mucosa: cytoprotection is not associated with preservation of the gastric mucosal barrier.
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 potassium ion (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 hemorrhagic erosions covering approximately 24% of the glandular mucosa. Prior topical application of PGE2 at doses of 25, 75, and 300 micrograms/kg significantly reduced the extent of hemorrhagic erosions. However, PG pretreatment did not produce a reduction in the effects of topical salicylate on either PD or net K+ efflux. Rather, 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. These results suggest that the mechanism of "cytoprotection" by PGE2 against salicylate-induced gastric damage is not a consequence of preservation of the gastric mucosal barrier.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015232:Dinoprostone; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000633:toxicity*
D011458:Prostaglandins E; D012459:Salicylates; D015232:Dinoprostone; D011188:Potassium