Facilitation by endogenous prostaglandins of capsaicin-induced gastric protection in rodents through EP2 and IP receptors

Koji Takeuchi, Shinichi Kato, Masanori Takeeda, Yoshihiro Ogawa, Masato Nakashima, Masahiro Matsumoto

研究成果: ジャーナルへの寄稿学術誌査読

50 被引用数 (Scopus)

抄録

We investigated the role that prostaglandins (PGs) and EP receptors play in facilitating the gastroprotective action of capsaicin against HCl/ethanol in rats and mice. Male Sprague-Dawley rats and C57BL/6 mice were used after 18 h of fasting. The animals were given HCl/ethanol (60% in 150 mM HCl) p.o. and killed 1 h later. Capsaicin or various EP agonists were given p.o. 30 min or i.v. 10 min before HCl/ethanol. In some cases, indomethacin or various EP agonists were given s.c. 30 min or i.v 10 min before capsaicin, respectively. Gastric lesions induced by HCl/ethanol were significantly inhibited by PGE2 as well as capsaicin. The effect of PGE2 was antagonized by ONO-AE-829 (EP1 antagonist), whereas the capsaicin action was mitigated by indomethacin as well as sensory deafferentation but not by ONO-AE-829. The generation of mucosal PGE2, was not affected by either capsaicin or sensory deafferentation, but was significantly inhibited by indomethacin. Although neither butaprost (EP2), ONO-NT-012 (EP3), nor 11-deoxy PGE1 (EP4) alone had any effect on HCl/ethanol-induced gastric lesions, only butaprost restored the protective action of capsaicin in the presence of indomethacin. Capsaicin provided a protective action against HCl/ethanol-induced gastric lesions in wild-type (+/+) mice in an indomethacin-sensitive manner, and this action was similarly observed in EP1 (-/-) and EP3 (-/-) mice but not in the animals lacking IP receptors. These results suggest that capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous PGs through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin.

本文言語英語
ページ(範囲)1055-1062
ページ数8
ジャーナルJournal of Pharmacology and Experimental Therapeutics
304
3
DOI
出版ステータス出版済み - 3月 1 2003
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学

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