Endothelin-1 Receptors in Rat Tissues: Characterization by Bosentan, Ambrisentan and CI-1020

DOI Web Site Web Site PubMed 被引用文献1件 参考文献9件 オープンアクセス
  • Yokoyama Yoshinari
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  • Osano Ayaka
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  • Hayashi Hideki
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  • Itoh Kunihiko
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  • Okura Takashi
    Laboratory of Drug Disposition & Pharmacokinetics, Faculty of Pharma-Science, Teikyo University
  • Deguchi Yoshiharu
    Laboratory of Drug Disposition & Pharmacokinetics, Faculty of Pharma-Science, Teikyo University
  • Ito Yoshihiko
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka
  • Yamada Shizuo
    Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka

この論文をさがす

抄録

The present study aimed to characterize comparatively endothelin-1 (ET-1) receptors in rat tissues by radioligand binding assay using [125I]ET-1 and to examine receptor binding after oral administration of bosentan. Significant amount of specific [125I]ET-1 binding was detected in the lung, heart, kidney, bladder and cerebral cortex of rats. ET-1, bosentan, ambrisentan, and CI-1020 inhibited specific [125I]ET-1 binding in these tissues in a concentration-dependent manner. The Hill coefficients of each agent in the rat lung and cerebral cortex and those of bosentan and ET-1 in the heart, kidney and bladder were close to unity, while the Hill coefficients of ambrisentan and CI-1020 in the heart, kidney and bladder were less than one. The nonlinear least squares regression analysis revealed the presence of high- and low-affinity ET-1 receptor sites in these tissues for ambrisentan and CI-1020. Oral administration of bosentan caused a dose-dependent decrease in specific [125I]ET-1 binding in the rat lung, kidney and bladder, suggesting significant binding of the tissue ET-1 receptors in vivo. In conclusion, it has been shown that a significant amount of pharmacologically relevant ET-1 receptors may exist in rat tissues and that ET-1 receptor antagonists such as bosentan at pharmacological doses may exert some pharmacological effects by binding these ET-1 receptors.

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (9)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ