BETA-ADRENERGIC RECEPTOR-MEDIATED REGULATION OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE IN C6 GLIOMA-CELLS - VINBLASTINE BLOCKADE OF ISOPROTERENOL INDUCTION
Persistent stimulation with isoproterenol [Ip] of the .beta. adrenergic receptor located in rat C6 glioma cell membranes results in a rapid rise in the cyclic[c]AMP content, an activation of soluble cAMP-dependent protein kinase, a translocation of catalytic subunits of the activated protein kinase to the nucleus and a delayed (3-4 h) increase of cAMP phosphodiesterase [PD] activity and .beta.-nerve growth factor content. The [PD] increase requires new RNA and protein synthesis. A pretreatment of the cells with vinblastine [VB] in doses that fail to change protein synthesis blocks the increase in PD activity elicited by IP: the ED50 of VB for this effect is 2.6 .times. 10-7 M. The simultaneous increase in .beta.-nerve growth factor content elicited by IP is not blocked by VB and does not require new RNA and protein synthesis. Intact microtubules are required to transfer the catalytic subunits of activated protein kinase from cytosol to the nucleus. Microtubules may be operative in facilitating communication between the cell membrane and the nucleus.