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 (COX(1) and COX(2)), 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 microM) enhanced the PGE(2) release (ACh-stimulated PGE(2) release) was mediated via intracellular Ca(2+) concentration ([Ca(2+)](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 COX(1)-selective inhibitor) inhibited ACh-stimulated PGE(2) release without any decrease in basal PGE(2) release. N-(2-Cyclohexyloxy-4-nitrophenyl) methanesulphonamide (NS398, 20 microM, a COX(2)-selective inhibitor) decreased basal PGE(2) release without any reduction of ACh-stimulated PGE(2) release. However, ionomycin (a Ca(2+) ionophore) increased PGE(2) release from antral mucosa in the presence of SC560 or NS398, suggesting that COX(1) and COX(2) are regulated by [Ca(2+)](i). These findings indicate that COX(1)-containing cells have ACh receptors but COX(2)-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 COX(2) of non-epithelial cells, and ACh-stimulated PGE(2) release is maintained by COX(1) of epithelial cells.
Shimamoto
Chikao
C
Central Research Laboratory (Nakahari Project), Osaka Medical College, 2-7 Daigaku-cho, Takatsuki 569-8686, Japan.
Nakanishi
Yoshihiko
Y
Katsu
Ken-ichi
K
Nakano
Takashi
T
Kubota
Takahiro
T
Mori
Hiroshi
H
Nakahari
Takashi
T
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D002934:Cinnamates; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; C085901:4-amylcinnamoylanthranilic acid; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D015759:Ionomycin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D015232:Dinoprostone; D000109:Acetylcholine; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin