title: Possible mechanism of induction of liver microsomal monooxygenases by phenobarbital.
abstract: A study has been made of a model of "consecutive" induction of microsomal monooxygenases following treatment with phenobarbital which was administered after maximal induction by 3-methylcholanthrene. It  has been found that in this "consecutive" system, notwithstanding the discontinuation of 3-methylcholanthrene, phenobarbital stimulates the further increase of the CO-binding hemoprotein content in the form of P-488. At the same time there is a considerable gain in the content of its high-spin species. An increase has been observed in the velocity of NADPH-dependent reduction of the CO-binding hemoprotein as well as a pronounced elevation in the activity of amino-pyrine N-demethylase. The data presented indicate that the location of the CO-peak of Na2S2O4-reduced hemoprotein is not the criterion of monooxygenase functional specificity; the latter may, possibly, be defined by the relation between the contents of the high-spin and low-spin species of the cytochrome. The possibility has been demonstrated of phenobarbital induction under conditions when the inducer-microsomal hemoprotein primary binding step is not involved, inasmuch as cytochrome P-448 lacks binding sites for phenobarbital. In this connection it is assumed that in the mechanism of phenobarbital induction of microsomal monooxygenases the activation of a portion of the genome and subsequent protein synthesis are effected by the substrate itself and not by the products of its primary metabolism in the microsomes.
mesh_terms: D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010105:Oxygenases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013053:Spectrophotometry
chemical_list: D003580:Cytochromes; D008748:Methylcholanthrene; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital