TY - JOUR T1 - The Effect of Phenobarbital on the Synthesis of Nascent Protein on Free and Membrane-Bound Polyribosomes of Normal and Regenerating Liver JF - Molecular Pharmacology JO - Mol Pharmacol SP - 701 LP - 710 VL - 8 IS - 6 AU - ROBERT I. GLAZER AU - ALAN C. SARTORELLI Y1 - 1972/11/01 UR - http://molpharm.aspetjournals.org/content/8/6/701.abstract N2 - The synthesis of nascent protein on free and membrane-bound polyribosomes or normal and regenerating liver was measured following a pulse injection of [3H]leucine into the portal vein of rats. Neither the pool size nor specific activity of leucine was markedly affected by the various experimental conditions. A single dose of phenobarbital (100 mg/kg) elevated maximally (2-2.3-fold) the synthesis of nascent peptide on membrane-bound polyribosomes 3-14 hr after treatment with the inducer, whereas formation of protein on free polyribosomes increased 1.6-fold only 5 hr after the barbiturate. Partial hepatectomy caused a 2-fold increase in the synthesis of nascent protein on membrane-bound polyribosomes as early as 1 hr after the operation. The rate of peptide synthesis on membrane-bound polyribosomes increased up to 3.5-fold over sham-operated controls 12 hr posthepatectomy. The formation of protein on free polyribosomes following partial hepatectomy was elevated approximately 2-fold 1-12 hr after the operation. When partially hepatectomized animals were treated 1 hr before surgery with a single dose of phenobarbital, no further increase in the synthesis of nascent protein occurred on either population of polyribosomes, suggesting (a) maximal translation in response to the stress of partial hepatectomy and (b) the competitive nature of hyperplasia and the functional process of protein synthesis on membrane-bound polyribosomes. Immunoprecipitation of pulse-labeled nascent protein on free and membrane-bound po1yribosomes with an antiglobulin to rat liver NADPH-cytochrome c reductase revealed a 2-fold elevation in the amount of reductase synthesized on membrane-bound polyribosomes 3-5 hr after phenobarbital administration; no concomitant change in the synthesis of nascent enzyme was noted on free polyribosomes. Although NADPH-cytochrome c reductase was equally distributed between the two populations of polyribosomes, the total concentration of enzyme was 20 times higher on membrane-bound polyribosomes than on free polyribosomes. ACKNOWLEDGMENTS The authors are indebted to Mrs. Rose Schulz for her expert preparation of samples for electron microscopy, and to Dr. Daniel Rudman for the amino acid analyses. ER -