On the Mechanism of Levosimendan-Induced Dopamine Release in the Striatum of Freely Moving Rats

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The Ca<sup>2+</sup> sensitizer levosimendan (LEV) improves myocardial contractility by enhancing the sensitivity of the contractile apparatus to Ca<sup>2+</sup>. In addition, LEV promotes Ca<sup>2+</sup> entry through L-type channels in human cardiac myocytes. In this study, which was performed using microdialysis, infusion of LEV at 0.25 μM for 160 min increased dopamine (DA) concentrations (up to fivefold baseline) in dialysates from the striatum of freely moving rats. Ca<sup>2+</sup> omission from the perfusion fluid abolished baseline DA release and greatly decreased LEV-induced DA release. Reintroduction of Ca<sup>2+</sup> in the perfusion fluid restored LEV-induced DA release. Chelation of intracellular Ca<sup>2+</sup> by co-infusing 1,2-bis (<i>o</i>-amino-phenoxy)ethane-<i>N</i>,<i>N</i>,<i>N'</i>,<i>N'</i>-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM, 0.2 mM) did not affect basal DA release and scarcely affected LEV-induced increases in dialysate DA. In addition, co-infusion of the L-type (Ca<sub>v</sub> 1.1 – 1.3) voltage-sensitive Ca<sup>2+</sup>-channel inhibitor nifedipine failed to inhibit LEV-induced increases in dialysate DA, which, in contrast, was inhibited by co-infusion of the N-type (Ca<sub>v</sub> 2.2) voltage-sensitive Ca<sup>2+</sup>-channel inhibitor ω-conotoxin GVIA. We conclude that LEV promotes striatal extracellular Ca<sup>2+</sup> entry through N-type Ca<sup>2+</sup> channels with a consequent increase in DA release.<br>

収録刊行物

  • Journal of pharmacological sciences

    Journal of pharmacological sciences 95(3), 299-304, 2004-07-20

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10013335047
  • 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
    7012005
  • 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  NDL  J-STAGE 
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