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Lubiprostone prevents NSAID‐induced small intestinal damage via prostaglandin EP4 receptors (840.7)
Author(s) -
Takeuchi Koji,
Hayashi Shusaku,
Amagase Kikuko,
Kurata Naoto
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.840.7
Subject(s) - lubiprostone , enteropathy , chemistry , downregulation and upregulation , medicine , receptor , pharmacology , antagonist , endocrinology , biochemistry , chronic constipation , constipation , disease , gene
We examined the effect of lubiprostone, a bicyclic fatty acid derived from PGE1 and a possible chloride channel type‐2 opener, on indomethacin (IM)‐induced small enteropathy and investigated the mechanisms involved, including the relationship to EP4 receptor. Methods: Male SD rats without fasting were given IM (10 mg/kg) s.c and killed 24 h later to examine hemorrhagic lesions developed in the small intestine. Lubiprostone (0.1 mg/kg) was given p.o. 30 min before IM treatment. Results: IM caused hemorrhagic lesions in the small intestine, accompanied by the upregulation of iNOS and TNFα mRNA expressions as well as enterobacterial invasion. Lubiprostone prevented the ulcerogenic response to IM, with concomitant inhibition of the upregulation of iNOS and TNFα expressions and bacterial invasion. These effects of lubiprostone were significantly abrogated by pretreatment of AE3‐208, an EP4 antagonist, but not CFTR(inh)‐172, a CFTR inhibitor. Conclusion: Lubiprostone prevents IM‐induced enteropathy via the EP4 receptor‐dependent mechanism, and this effect may be associated with suppression of the expression of inflammatory mediators such as iNOS and TNFα. In addition, it is unlikely that CFTR chloride channels contribute to the protective effect of lubiprostone against NSAID‐induced enteropathy.