Wortmannin Inhibits the Increase in Myofilament Ca2+ Sensitivity Induced by Cross-Talk of Endothelin-1 With Norepinephrine in Canine Ventricular Myocardium

• Chu Li

  Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Japan Department of Pharmacology, Hebei Medical University, China

• Norota Ikuo

  Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Japan

• Ishii Kuniaki

  Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Japan

• Endoh Masao

  Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Japan

抄録

Endothelin-1 (ET-1) modulates cardiac contractility by cross-talk with norepinephrine (NE) in canine ventricular myocardium. The present experiments were performed to investigate the influence of wortmannin that has inhibitory action on phosphatidylinositol 3-kinase (PI3-K) (IC₅₀ = 3 nM) and myosin light chain kinase (MLCK) (IC₅₀ = 200 nM) on Ca²⁺ signaling and the inotropic effects of ET-1 induced by cross-talk with NE. Experiments were carried out in isolated canine ventricular trabeculae and indo-1/AM–loaded single ventricular cardiomyocytes. ET-1 alone elicited a transient small negative inotropic effect (NIE). In the presence of NE at low (1 – 10 nM) and high (100 nM) concentrations, ET-1 induced a long-lasting positive inotropic effect (PIE) or a marked sustained NIE, respectively. Wortmannin up to 300 nM did not affect the contractility; and at 1 μM and higher, it decreased the basal contraction without suppressing Ca²⁺ transients. Wortmannin (1 μM) inhibited the long-lasting PIE of ET-1 without affecting the ET-1–induced increase in Ca²⁺ transients. Wortmannin at the same concentration did not affect the ET-1–induced transient and sustained NIE and the PIE mediated by β-adrenoceptor stimulation. These results imply that wortmannin exerts selective inhibitory action on the increase in myofilament Ca²⁺ sensitivity induced by cross-talk of ET-1 with NE probably through an inhibition of MLCK in canine ventricular myocardium.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 109 (2), 193-202, 2009

  公益社団法人 日本薬理学会

キーワード

• inotropic effect
• Ca²⁺ transient
• endothelin-1
• norepinephrine
• wortmannin

詳細情報

• CRID: 1390001205180200704
• NII論文ID: 10025734286
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.08228fp
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 10160565
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10160565
• Web Site: https://search.jamas.or.jp/link/ui/2009188743
• 本文言語コード: en
• データソース種別:
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  • NDL
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