Molecular Pharmacology, Vol 9, 259-265, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of [6-¹⁴]Orotic Acid Incorporation into the Cytosine Moiety of the Ribonucleic Acid of Rat Liver Cytoplasmic Ribosomes after Phenobarbital Administration

¹ Institute of Pharmacology, Czechoslovak Academy of Sciences, 12800 Prague 2, Albertov 4, Czechoslovakia

Administration of phenobarbital in drinking water (1 g/liter) to rats produces a disproportionate incorporation of [6-¹⁴C]orotic acid into the pyrimidine nucleotides of the RNA of the isolated cytoplasmic ribosomes and also tRNA. The specific activity of uridylic acid is slightly decreased, whereas the specific activity of cytidylic acid is markedly lowered. After correction for the increased rRNA content in hypertrophic liver following the administration of phenobarbital, the specific activity of uridylic acid is only slightly increased, although the decrease of the value for cytidylic acid is still apparent. The decreased incorporation of labeled orotic acid is also evident in the cytosine components of the nucletoide pool. The observed differences in the incorporation of [6-¹⁴C]orotic acid into both pyrimidine nucleotides of rRNA depend on the length of application of the drug: the largest differences are observed between the 6th and 20th days of phenobarbital administration. A slight convergence of the values occurs during the subsequent phase of the application.

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ACKNOWLEDGMENTS The authors gratefully acknowledge helpful discussions with Professor J. koda.