Effect of Tranilast on Endothelin-Induced Bronchoconstriction in Guinea Pigs
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概要
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Tranilast, an anti-asthmatic drug with anti-allergic properties, inhibited endothelin (ET)-induced asthmatic like respiratory obstruction in guinea pigs when administered orally at 200 mg/kg 1 h prior to the intravenous injection of ET. ET also caused a bronchoconstriction detected as an increase in inflation pressure in Konzett-Rossler apparatus. Tranilast (200 mg/kg, p.o. 1 h before ET) inhibited ET-induced increased inflation pressure. ET-induced bronchoconstriction detected as an increase in inflation pressure was clearly inhibited by the administration of indomethacin (used as a reference drug) at doses of 1 and 5 mg/kg 30 min prior to onset of the reaction. In addition to the above in vivo experiments, tranilast at concentrations between 10^<-5> and 10^<-4> g/ml inhibited ET-induced contraction of isolated guinea pig tracheal muscle, whereas indomethacin did not affect this in vitro response. In order to elucidate the inhibitory mechanism of tranilast on ET-induced bronchoconstriction, the effects in Ca^<2+>-free medium and on ET-induced histamine and prostaglandin F_<2α> release from tracheal muscle were investigated. Consequently, tranilast did not affect ET-induced contraction of guinea pig tracheal muscle in Ca^<2+>-free Tyrode's solution and ET induced neither histamine nor PGF_<2α> release. These results suggest that tranilast inhibits ET-induced bronchoconstriction by inhibiting the ET-induced calcium influx into tracheal muscle.
- 公益社団法人日本薬学会の論文
著者
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NAGAI Hiroichi
Department of Pharmacology, Gifu Pharmaceutical University
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Koda A
Gifu Pharmaceutical Univ. Gifu Jpn
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SUDA Hiroshi
Department of Astronomy, The University of Tokyo
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Sugiura H
Gifu Pharmaceutical Univ. Gifu
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KODA AKIHIDE
Department of Pharmacology, Gifu College of Pharmacy
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Nagai Hiroichi
Department Of Clinical Pharmacology Gifu Pharmaceutical University
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Koda Akihide
Department Of Pharmacology Gifu College Of Pharmacy
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KITAGAKI Kunihiko
Department of Hygiene, Dokkyo University School of Medicine
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Nagai Hiroichi
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Sugiura Haruo
Department Of Pharmacology Gifu Pharmaceutical University
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Suda Hiroshi
Department of Applied Science, Faculty of Engineering, Tohoku University
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