Ouabain-Induced Cell Proliferation in Cultured Rat Astrocytes.

  • Murata Yosuke
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Matsuda Toshio
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Tamada Kazuko
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Hosoi Rie
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Asano Shoichi
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Takuma Kazuhiro
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Tanaka Koh-ichi
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>
  • Baba Akemichi
    <I>Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University</I>

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  • Ouabain Induced Cell Proliferation in C

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Abstract

Ouabain markedly stimulated not only [3H]thymidine incorporation but also [3H]uridine incorporation into astrocytes. The effects were observed at 36-48 hr and 12-72 hr after addition of ouabain, respectively. The dose-response curves were both bell-shaped types with a peak at 10−3 M for thymidine incorporation and 2 × 10−3 M for uridine incorporation. Ouabain increased cell number as determined by an assay using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and by a method using a hemocyiometer. Low concentration of external K+ mimicked the effect of ouabain in stimulating [3H]-thymidine incorporation, and high concentration of external K+ blocked the effect of ouabain. In contrast to astrocyies, ouabain did not stimulate [3H]thymidine incorporation into C6 glioma and fibroblast cells. The effect of ouabain on [3H]thymidine incorporation in astrocyies was dependent on external Ca2+, and it was blocked by cycloheximide. These findings indicate that prolonged Na+, K+-ATPase inhibition causes cell proliferation in cultured astrocyies in cell-specific and Ca2+-dependent manners.

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