Evidence that adaptive cytoprotection in rats is not mediated by prostaglandins.

We investigated the proposition that adaptive cytoprotection (enhanced gastric mucosal integrity) caused by exposure to 20% ethanol in rats is mediated by endogenous prostaglandin synthesis. Experiments were performed both without and with indomethacin sufficient to inhibit ex vivo release of prostaglandin E2 by 56% +/- 9% (2.5 mg/kg) or 86% +/- 4% (10 mg/kg). Twenty percent ethanol significantly reduced both macroscopic and histologic signs of injury caused by subsequent exposure to 100% ethanol whether or not the rats were pretreated with indomethacin. Twenty percent ethanol itself caused extensive superficial disruption of the surface epithelium, so that about half of the mucosa was covered by desquamated debris, but did not stimulate prostaglandin release. We conclude that adaptive cytoprotection still occurs after doses of indomethacin sufficient to cause a profound depression of prostaglandin E2 release. The possibility that it could be due to formation of a protective covering of surface debris is worth further investigation.