beta Adrenergic receptor-mediated regulation of cyclic nucleotide phosphodiesterase in C6 glioma cells: vinblastine blockade of isoproterenol induction.

Persistent stimulation with isoproterenol of the beta adrenergic receptor located in C6 glioma cell membranes results in a rapid rise in the cyclic AMP content, an activation of soluble cyclic AMP-dependent protein kinase, a translocation of catalytic subunits of the activated protein kinase to the nucleus and a delayed (3--4 hr later) increase of cyclic AMP phosphodiesterase activity and beta-nerve growth factor content. The phosphodiesterase increase requires new RNA and protein synthesis. A pretreatment of the cells with vinblastine in doses that fail to change protein synthesis blocks the increase in phosphodiesterase activity elicited by isoproterenol: the ED50 of vinblastine for this effect is 2.6 x 10(-7) M. In contrast, the simultaneous increase in beta-nerve growth factor content elicited by isoproterenol is not blocked by vinblastine and does not require new RNA and protein synthesis. We conclude that intact microtubules are required to transfer the catalytic subunits of activated protein kinase from cytosol to the nucleus. Hence microtubules may be operative in facilitating communication between the cell membrane and the nucleus.