Selective induction and inhibition of the components of 7-ethoxycoumarin O-deethylase activity in the rat.
Treatment of rats with 3-methylcholanthrene increased Vmax of the high-affinity component of 7-ethoxycoumarin O-deethylase activity 60-fold. There was also an increase in Vmax of the low-affinity component. Treatment with phenobarbitone increased Vmax of the high-affinity component six-fold whilst not affecting the Km of this component. Modest changes were also observed in the kinetics of the low-affinity component. Following treatment with 3-methylcholanthrene, the sensitivity of both the high- and low-affinity components of activity to inhibition by alpha-naphthoflavone was considerably increased, with the IC50 decreasing from greater than 250 microM to less than 10 microM in both instances. Following treatment with phenobarbitone, the sensitivity of the low-affinity component to inhibition by metyrapone was considerably increased, with the IC50 decreasing from greater than 1000 microM to 96 microM. There was also a modest, but significant, increase in sensitivity of the high-affinity component to metyrapone. These results indicate that both components of 7-ethoxycoumarin O-deethylase activity are catalysed by more than one form of cytochrome P-450.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001571:Benzoflavones; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D010634:Phenobarbital; D008797:Metyrapone