Prostaglandin E2 release in gastric antral mucosa of guinea-pigs: basal PGE2 release by cyclo-oxygenase 2 and ACh-stimulated PGE2 release by cyclo-oxygenase 1.

Prostaglandin E-2 (PGE(2)), which is generated by two isoforms of cyclo-oxygenase (COX1 and COX2), is a key mediator in gastric mucosal defense. In the present study, antral mucosa of guinea-pigs was incubated with various agonists or antagonists in a medium, the PGE(2) concentration of which was measured using a PGE(2) EIA kit. Prostaglandin E-2 was released from the antral mucosa spontaneously (basal PGE(2) release) and acetylcholine (ACh, 10 mu M) enhanced the PGE(2) release (ACh-stimulated PGE(2) release) was mediated via intracellular Ca2+ concentration ([Ca2+](i)). Arachidonic acid enhanced both forms of PGE(2) release, and a phospholipase A(2) inhibitor (amylcinnamoyl anthranilic acid) and COX inhibitors (acetylsalicylic acid and indomethacin) decreased them. 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazol (SC560, 100 nM, a COX1-selective inhibitor) inhibited ACh-stimulated PGE(2) release without any decrease in basal PGE(2) release. N-(2-Cyclohexyloxy-4-nitrophenyl) methanesulphonamide (NS398, 20 mu M, a COX2-selective inhibitor) decreased basal PGE(2) release without any reduction of ACh-stimulated PGE(2) release. However, ionomycin (a Ca2+ ionophore) increased PGE(2) release from antral mucosa in the presence of SC560 or NS398, suggesting that COX1 and COX2 are regulated by [Ca2+](i). These findings indicate that COX1-containing cells have ACh receptors but COX2-containing cells do not. Moreover, in isolated antral epithelial cells, SC560 decreased basal and ACh-stimulated PGE(2) release, but NS398 did not. In conclusion, in antral mucosa, basal PGE(2) release is mainly maintained by COX2 of non-epithelial cells, and ACh-stimulated PGE(2) release is maintained by COX1 of epithelial cells.