Molecular Pharmacology, Vol 15, 115-130, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Nuclear Translocation of Cyclic AMP-Dependent Protein Kinase Subunits During the Transsynaptic Activation of Gene Expression in Rat Adrenal Medulla

¹ Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032

In rat adrenal medulla gene expression can be activated by transsynaptic stimulation of nicotinic receptors via an increase of the adenosine 3',5' monophosphate content (cyclic AMP). This increase activates the cyclic AMP-dependent ATP: protein phosphotransferase (protein kinase) of adrenal medulla. Type I and II cyclic AMP-dependent protein kinases are present in the adrenal medulla cytosol; both enzymes were activated and dissociated into regulatory and catalytic subunits following the increase of medullary cyclic AMP content elicited transsynaptically. However only the cytosol content of Type I cyclic AMP-dependent protein kinase but not that of Type II enzymes decreases for several hours following persistent activation of nicotinic receptors. This decrease was associated with the appearance of catalytic subunits of cyclic AMP-dependent protein kinase in nuclei. The phosphorylation of endogenous nuclear protein was increased after the redistribution of the catalytic subunits of cyclic AMP-dependent protein kinase elicited by the persistent stimulation of nicotinic receptors. A similar increase of nuclear protein phosphorylation was elicited also "in vitro" by incubating nuclei of adrenal medulla with cyclic AMP and cyclic AMP-dependent Type I protein kinase; in contrast, the incubation of these nuclei with Type II protein kinase failed to increase the phosphorylation of nuclear proteins. For comparison, the fate of catalytic subunits of cyclic AMP-dependent protein kinase of pineal gland cytosol was studied following a sustained transsynaptic activation of protein kinase. Only Type II cyclic AMP-dependent protein kinase is present in pineal cytosol. This enzyme was activated and dissociated following the increase of cyclic AMP content elicited by isoproterenol, but its catalytic subunits failed to translocate into the pineal cell nuclei suggesting that translocation into nuclei is not a generalized property of cyclic AMP-dependent protein kinase.