Molecular Pharmacology, Vol 13, 426-434, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Acute and Chronic Phenobarbital Treatment on the Activity of Rat Liver Deoxyribonucleic Acid-Dependent Ribonucleic Acid Polymerases

¹ Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85724

Eukaryotic DNA-dependent RNA polymerases (I, II, and III) have a diurnal rhythm which is altered by the administration of a single dose of phenobarbital (60 mg/kg) in young rats on a 12-hr light, 12-hr dark lighting schedule. Constant lighting essentially abolished the pattern of activity of RNA polymerases I and III and produced a minor variation in the rhythm of RNA polymerase II. Administration of phenobarbital (100 mg/kg) to animals maintained in constant light altered the diurnal rhythm of RNA polymerase II but did not change the activities of RNA polymerases I and III. No significant alteration in the activity of any of the RNA polymerases was observed by comparison of phenobarbital-treated rats with NaCl-treated controls under either normal or constant lighting when individual points across the 24-hr period were averaged. Under both lighting protocols phenobarbital produced an increase in plasma corticosteroid 6-9 hr after administration, which could not be correlated with changes in the activities of the RNA polymerases. No relationship could be established between the normal pattern of plasma corticosteroid and RNA polymerase activities. Chronic administration of phenobarbital (100 mg/kg/day) did not stimulate nuclear RNA polymerases on days 1-4 of administration; only on day 5 was stimulation observed. The 5-day average RNA polymerase II activity was significantly depressed in phenobarbital-treated compared with control animals. No change in liver RNA polymerases was observed in older rats given phenobarbital in their drinking water (1 mg/ml) for 10 days. The results suggest that hypertrophy induced in the liver by phenobarbital is not accompanied by a discernible increase in hepatic transcription as manifested by increases in RNA polymerase activity, and support other studies in which decreased turnover and/or stabilization of hepatic RNA was found.

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ACKNOWLEDGMENTS The expert technical assistance of Sandra Burt, Colleen Bentley, and Dorohy Warren is gratefully acknowledged. The authors also thank Dr. George Hedge of the Department of Physiology at the University of Arizona College of Medicine for performing the corticosteroid assays.