Induction of Glutamine Synthetase by Dibutyryl Cyclic AMP in C‐6 Glioma Cells

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Abstract
Glutamine synthetase increased in C-6 [rat] glioma cells as a result of increasing culture passage and N-6,2''-O-dibutyryl cAMP (dbcAMP) treatment. At low passage dbcAMP produced a 2.5-fold increase in glutamine synthetase activity per unit of cellular protein. At high passage control glutamine synthetase was approximately double that seen at low passage, but dbcAMP produced an additional 65% increase. Lactate dehydrogenase activity increased by dbcAMP treatment at both low and high passage, but culture passage produced no change in the lactate dehydrogenase. With increasing culture passage, the ratio of cellular protein to DNA doubled. Expression of data per unit of protein tended to minimize the apparent changes in activity. The maximum increase in glutamine synthetase activity produced by both dbcAMP and increasing culture passage and expressed on a DNA basis was 5.6-fold. The increase in glutamine synthetase activity was generally linear during the first 20 h of drug treatment, after which enzyme activity remained nearly constant up to 72 h. Of the dbcAMP, .gtoreq. 90% remained in the medium at the end of 48-h cell exposure. 8-Br-cAMP increased glutamine synthetase activity of C-6 cells, but n-butyrate did not. Isoproterenol, which increases cAMP in C-6 cells, increased glutamine synthetase activity. The effect of isoproterenol on glutamine synthetase was inhibited by the .beta.-adrenergic blocking agent sotalol. Cycloheximide (10 .mu.g/ml) inhibited the dbcAMP effect on glutamine synthetase activity and also decreased the control enzyme activity by 60%.