Pharmacological Evidence for Involvement of Phospholipase D, Protein Kinase C, and Sodium-Calcium Exchanger in α-Adrenoceptor-Mediated Negative Inotropy in Adult Mouse Ventricle

  • Nishimaru Kazuhide
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Tanaka Yoshio
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Tanaka Hikaru
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Shigenobu Koki
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences

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タイトル別名
  • Pharmacological Evidence for Involvement of Phospholipase D, Protein Kinase C, and Sodium-Calcium Exchanger in .ALPHA.-Adrenoceptor-Mediated Negative Inotropy in Adult Mouse Ventricle
  • Pharmacological Evidence for Involvement of Phospholipase D Protein Kinase C and Sodium Calcium Exchanger in アルファ Adrenoceptor Mediated Negative Inotropy in Adult Mouse Ventricle

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The intracellular signalling pathway for α-adrenoceptor-mediated negative inotropy was studied pharmacologically in isolated adult mouse ventricle. The negative inotropy was inhibited by GF-109203X, a nonselective protein kinase C inhibitor. Phorbol 12-myristate 13-acetate also produced sustained negative inotropy, which was inhibited by KB-R7943, a Na+/Ca2+ exchanger inhibitor. The α-adrenoceptor-mediated negative inotropy was augmented by RHC-80267, a diacylglycerol lipase inhibitor, but was inhibited either by C2-ceramide, a phospholipase D inhibitor, and high concentration of propranolol (50 μM), which inhibits phosphatidate phosphohydrolase. The inotropy was not affected by U-73122, a phospholipase C inhibitor. Lavendustin-A, a tyrosine kinase inhibitor, also inhibited the negative inotropy. These findings suggest that α-adrenoceptor-mediated negative inotropy in adult mouse ventricle is mediated by activation of tyrosine kinase, the phospholipase D-phosphatidate phosphohydrolase pathway, and protein kinase C.<br>

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