Received May 5, 2006
Revised July 11, 2006
Accepted after revision August 29, 2006
GI & Epithelial Physiology [230]
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Prostaglandin E2 release from gastric antral mucosa of guinea pigs: essential role of COX2 under physiological condition
Chikao Shimamoto 1,
Yoshihiko Nakanishi 1,
Ken-ichi Katsu 1,
Takashi nakano 2,
Takahiro Kubota 3,
Hiroshi Mori 3,
Takashi Nakahari 3*
1 Dept of Internal Medicine, Osaka Medical College
2 Dept of Microbiology, Osaka Medical College
3 Osaka Medical College
* To whom correspondence should be addressed. E-mail: takan{at}art.osaka-med.ac.jp.
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Abstract |
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Prostaglandin E2 (PGE2), which is generated by two isoforms of cyclooxygenase (COX1 and COX2), is a key mediator in gastric mucosal defense under physiological and pathophysiological conditions. In the present study, antral mucosa of guinea pigs was incubated with various agonists or antagonists in a medium, PGE2 concentration of which was measured using a PGE2 EIA kit. PGE2 was released from the antral mucosa spontaneously (basal PGE2 release) and acetylcholine (ACh, 10 µM) enhanced PGE2 release (ACh-stimulated PGE2 release) mediated via an increase in intracellular Ca2+ concentration ([Ca2+]i). Arachidonic acid enhanced PGE2 releases, and PLA2 inhibitor (amylcinnamoyl anthranilic acid) and COX inhibitors (acetylsalicylic acid and indomethacin) inhibited them. SC560 (100 nM, a COX1-selective inhibitor) inhibited ACh-stimulated PGE2 release without any decrease in basal PGE2 release. NS398 (20 µM, a COX2-selective inhibitor) decreased basal PGE2 release without any inhibition of ACh-stimulated PGE2 release. However, ionomycin (a Ca2+ ionophore) increased PGE2 release from antral mucosa with SC560 or NS398, suggesting that COX1 and COX2 are activated by an [Ca2+]i increase. These indicate that COX1-containig cells have ACh receptors but COX2-containing cells do not. Moreover, in isolated antral epithelial cells, SC560 inhibited PGE2 release with or without ACh, but NS398 did not. In conclusion, in antral mucosa, basal PGE2 release is mainly maintained by COX2 of nonepithelial cells, and ACh-stimulated PGE2 release is maintained by COX1 of epithelial cells.
Key Words:
Acetylcholine, Gastrointestinal tract, Prostaglandin