Cell cycle changes in the adenylate cyclase of C6 glioma cells.

Abstract

The adenylate cyclase of C6 [rat] glioma cell cultures was characterized for sensitivity to the .beta.-adrenergic agonist isoproterenol, as well as fluoride, and GTP as a function of the cell cycle. The mitotic phase of the cell cycle was emphasized because the basal cellular cAMP level and the intact C6 cell''s capacity to accumulate cAMP in response to isoproterenol decreased during mitosis. Basal and stimulated adenylate cyclase activities in mitotic cells were decreased relative to the enzyme activities in the G1, S and G2 phases of the cell cycle. Analysis of the .beta.-adrenergic receptor using the radioligand (-)[3H]dihydroalprenolol showed that neither ligand affinity nor receptor density changed during the cell cycle, indicating that the reduced adenylate cyclase activity of the mitotic C6 cell was not caused by alterations in this hormone receptor. The reduction in the mitotic cell''s basal adenylate cyclase activity was more prominent than the decrease in isoproterenol-, fluoride- or GTP-stimulated activities, suggesting that the effectiveness of these enzyme activators (i.e., the efficiency of the coupling mechanism) was not attenuated during mitosis. The intrinsic catalytic capacity (not the .beta.-adrenergic receptor or the coupling mechanism) of the C6 adenylate cyclase complex is reduced during mitosis and contributes to the mitotic cell''s inability to accumulate and maintain the cAMP concentration at the interphase level.