Prostaglandin E inhibits indomethacin-induced gastric lesions through EP-1receptors

Backgrounds and Aims: We examined the effect of various prostaglandin E (PG E) analogs specific to EP receptor subtypes on indomethacin-induced gastric lesions in rats and investigated which EP receptor subtype is involved in the protective action of PGE(2) using EP-receptor knockout mice. Methods: G astric lesions were induced by subcutaneous administration of indomethacin (35 mg/kg). Gastric motility was measured using a balloon method, while neu trophil chemotaxis determined using a Boyden chamber. Results: Indomethacin -induced gastric lesions were significantly prevented by PGE(2) as well as atropine, and the former effect was mimicked by sulprostone (EP1/EP3) and 1 7-phenyl PGE(2) (EP1) and antagonized by an EP1 antagonist, ONO-AE-829. Nei ther butaprost (EP2), ONO-NT-012 (EP3) nor 11-deoxy PGE(1) (EP3/ EP4) showe d any protection on the lesions. Indomethacin caused a marked increase in g astric motility; the response preceded the onset of lesions and was inhibit ed by atropine as well as PGE derivatives acting as EP1 receptors. Neutroph il chemotaxis was inhibited by PGE(2), butaprost and slightly by 11-deoxy P GE(1), but not by either 17-phenyl PGE(2), ONO-NT-012 or atropine. In addit ion, indomethacin caused damage similarly in both wild-type and knockout mi ce lacking EP1 or EP3 receptors, yet the protective action of PGE(2) was ob served in wild-type and EP3 receptor knockout mice but totally disappeared in mice lacking EP1 receptors. Conclusion: PGE(2) inhibits indomethacin-ind uced gastric lesions, through EP1 receptors, and this effect may be functio nally associated with inhibition of gastric motility but not of neutrophil activation/migration. Copyright (C) 2001 S. Karger AG, Basel.