Molecular Pharmacology, Vol 12, 514-518, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Trans-synaptic Regulation of Ribonucleic Acid Biosynthesis 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 the increase in activity of afferent cholinergic axons elicited by exposure to 4° for 4 hr augmented the incorporation of [³H]uridine into RNA. This change began 6 hr after stimulus application, reached a maximum at 8-10 hr, and was terminated by 16 hr. This increase preceded that of [³H]leucine incorporation into tyrosine hydroxylase, but followed translocation of the catalytic units of adenosine cyclic 3',5'-monophosphate-dependent histone kinase from the medullary cytosol to the nuclei. Adrenal denervation blocked histone kinase translocation and the stimulation of [³H]uridine incorporation into RNA and of [³H]leucine into tyrosine hydroxylase and other proteins elicited by cold exposure. RNA synthesis in nuclei isolated from the adrenal medullae of rats exposed to cold was greater than in medullae from normal rats; this increase was associated with stimulation of RNA synthesis dependent on RNA polymerase II, the enzyme responsible for the synthesis of RNA containing polyadenylic acid, which includes messenger RNA. The incorporation of [³H]uridine into poly(A)-containing RNA in vivo was significantly higher in the intact medulla than in the contralateral denervated medulla 8 hr after exposure to cold. It can be inferred that the trans-synaptic stimulation of RNA synthesis enhances primarily the transcription of new messenger RNA, which seem to control the translation of tyrosine hydroxylase and other medullary proteins.

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