Molecular Pharmacology, Vol 12, 820-831, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Phenobarbital-Induced Increases in Methylation of Ribosomal Precursor Ribonucleic Acid

¹ Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

In young adult male rats killed either 6 or 16 hr after a single intraperitoneal injection of phenobarbital (100 mg/kg) on 0.9% NaCl, hepatic nucleolar RNA methyltransferase activity and nucleolar RNA polymerase activity were measured as well as labeling of microsomal RNA in vivo. Nucleolar RNA methyltransferase activity was assayed, using isolated nucleoli, by the incorporation of S-adenosyl[³H]methionine into RNA. RNA polymerase activity was determined in a similar manner by measuring [³H]UTP incorporation. Incorporation in vivo of [³H]orotic acid was used in the cytoplasmic microsomal RNA-labeling studies. By 6 and 16 hr after phenobarbital, incorporation of methyl label into RNA increased by 29% and 36%, respectively. Six hours after a single intraperitoneal injection of phenobarbital, nucleolar RNA polymerase activity was unchanged. Six hours after phenobarbital, incorporation in vivo of [³H]orotic acid into cytoplasmic microsomal 18 S and 28 5 RNA was stimulated by approximately 50%. The increase in cytoplasmic RNA after phenobarbital administration appears to result from increased stability of nucleolar ribosomal precursor (45 S) RNA due to enhanced methylation rather than from an increase in transcription of 45 S RNA.

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ACKNOWLEDGMENTS We are grateful to Dr. S. T. Jacob for helpful discussions during the course of this work, and to Mr. Howard Beittenmiller for technical assistance.