Ouabain-induced cell proliferation in cultured rat astrocytes.
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 x 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 hemocytometer. 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 astrocytes, ouabain did not stimulate [3H]thymidine incorporation into C6 glioma and fibroblast cells. The effect of ouabain on [3H]thymidine incorporation in astrocytes 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 astrocytes in cell-specific and Ca(2+)-dependent manners.
Murata
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Matsuda
T
T
Tamada
K
K
Hosoi
R
R
Asano
S
S
Takuma
K
K
Tanaka
K
K
Baba
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism
D002316:Cardiotonic Agents; D010042:Ouabain; D012313:RNA; D007334:Insulin-Like Growth Factor I; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase; D013936:Thymidine