Ca^<2+>-Releasing Effect of Ceriastatin on the Sarcoplasmic Reticulum of Mouse and Rat Skeletal Muscle Fibers

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We analyzed the effect of HMG-CoA reductase inhibitors on Ca<sup>2+</sup> release from the sarcoplasmic reticulum (SR) using chemically skinned skeletal muscle fibers from the mouse and the rat. Cerivastatin (>20 μM) released Ca<sup>2+</sup> from the SR, while pravastatin showed only a little effect. The rates of Ca<sup>2+</sup> release were increased by cerivastatin at all Ca<sup>2+</sup> concentrations tested. Cerivastatin-induced Ca<sup>2+</sup> release in the presence of Ca<sup>2+</sup> was affected by adenosine monophosphate, Mg<sup>2+</sup>, and procaine in essentially the same way as for caffeine-induced Ca<sup>2+</sup> release. The Ca<sup>2+</sup>-uptake capacity of the SR was reduced after co-treatment with ryanodine and cerivastatin at pCa 6.0 to a much greater extent than with ryanodine alone. Thus, cerivastatin-induced Ca<sup>2+</sup> release in the presence of Ca<sup>2+</sup> must be a result of the activation of the Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release (CICR) mechanism of the ryanodine receptor. However, even when CICR was maximally inhibited by Mg<sup>2+</sup> and procaine, or in the practical absence of Ca<sup>2+</sup> (pCa >8), cerivastatin still caused Ca<sup>2+</sup> release. These results indicate that cerivastatin causes Ca<sup>2+</sup> release also by activating some other mechanism(s) in addition to the activation of CICR. Either or both of these effects might be related to its adverse effect, rhabdomyolysis.<br>

収録刊行物

  • Journal of pharmacological sciences

    Journal of pharmacological sciences 93(3), 279-288, 2003-11-01

    The Japanese Pharmacological Society

参考文献:  37件中 1-37件 を表示

被引用文献:  4件中 1-4件 を表示

各種コード

  • NII論文ID(NAID)
    10012544959
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    6757868
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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