Molecular Pharmacology, Vol 6, 540-547, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Metabolism of Ribonucleic Acid in Rat Liver after Phenobarbital Administration

¹ Departments of Pharmacology and Oral Biology, The University of Michigan Medical and Dental Schools, Ann Arbor, Michigan 48104

Incorporation of orotic acid-5-³H (100-200 µCi) into hepatic nuclear and cytoplasmic RNA extracted from purified nuclei or cytoplasmic fractions and separated on linear sucrose gradients was determined after intraperitoneal administration of phenobarbital (75 mg/kg) to rats. Pulses of 1-, 2-, 4-, and 12-hr duration were administered 2 hr after injection of phenobarbital or 0.9% NaCl in order to examine alterations in cytoplasmic RNA metabolism early in the induction process, i.e., before any marked increase occurred in the levels of microsomal drug-metabolizing enzymes. The data indicated that there was a 20-30% increase above controls in the specific activity of 28 S and 18 S ribosomal RNA, which became apparent after a 2-hr pulse dose of labeled precursor administered 2 hr after phenobarbital treatment, and which was maintained for 12 hr. The augmented labeling appeared to be restricted to ribosomal RNA species. Analysis of nuclear RNA after pulses of 1, 2, and 4 hr, given 2 hr after phenobarbital, indicated that there was no detectable increase in synthesis of ribosomal RNA or ribosomal RNA precursors. It is suggested that phenobarbital may enhance the stability of hepatic ribosomal RNA or increase the "processing" and transport of this substance to the cytoplasm, and that these events, which occur early in the induction process, may be involved in the elevation of microsomal oxidase activity observed after phenobarbital administration.

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ACKNOWLEDGMENT The authors wish to thank Mrs. Cynthia Rainey for her excellent technical assistance and for her help in the preparation of the manuscript.