Molecular Pharmacology, Vol 2, 171-186, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Studies on the Mechanism of Drug-Induced Microsomal Enzyme Activities

V. Phenobarbital Stimulation of Endogenous Messenger RNA and Polyuridylic Acid-Directed L-[¹⁴C]-Phenylalanine Incorporation

¹ Carcinogenesis Studies Branch, National Cancer Institute, Laboratory of Pharmacology, National Heart Institute, Bethesda, Maryland, and Department of Pharmacology, George Washington University Medical School, Washington, D.C.

The in vivo administration of phenobarbital increases amino acid incorporation in rat liver microsomes in vitro.

1. The increased incorporation is observed with different amino acids and is not due to changes in cofactor level, amino acid concentration, or factors present in the cell sap.

2. Microsomes from phenobarbital-treated rats are more active in L-[¹⁴C]-phenylalanine incorporation in the absence of polyuridylic acid. However, L-[¹⁴C]-phenylalanine incorporation is stimulated to the same extent by polyuridylic acid in microsomes from control and phenobarbital-treated rats. In contrast, after the removal of endogenous messenger RNA the microsomes from phenobarbital-treated rats are more than twice as sensitive as control microsomes to polyuridylic acid-directed L-[¹⁴C]-phenylalanine incorporation. This appears due to a phenobarbital-induced increase in both the endogenous microsomal messenger RNA content and the number of microsomal binding sites for messenger RNA. No difference in amino acid incorporation is observed in ribosomes from control and phenobarbital-treated rats, indicating that deoxycholate-soluble factors, presumably components of the endoplasmic reticulum, are important in protein synthesis and are altered by phenobarbital.

3. Microsomes from phenobarbital-treated rats contain a relatively greater proportion of membrane-bound ribosomes compared to free ribosomes.

Note:
ACKNOWLEDGMENTS We wish to acknowledge the valuable technical assistance of Mr. Haywood Waters.

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