TY - JOUR T1 - Facilitation by Endogenous Prostaglandins of Capsaicin-Induced Gastric Protection in Rodents through EP2 and IP Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1055 LP - 1062 DO - 10.1124/jpet.102.044156 VL - 304 IS - 3 AU - Koji Takeuchi AU - Shinichi Kato AU - Masanori Takeeda AU - Yoshihiro Ogawa AU - Masato Nakashima AU - Masahiro Matsumoto Y1 - 2003/03/01 UR - http://jpet.aspetjournals.org/content/304/3/1055.abstract N2 - 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 PGE2was 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. The American Society for Pharmacology and Experimental Therapeutics ER -