Phenacetin O-deethylase activity of the rat: strain differences and the effects of enzyme-inducing compounds.
Phenacetin O-deethylase activity in microsomal fractions from liver of DA and Fischer rats has been determined. No major sex or strain differences were found. Kinetic analysis revealed two major components of O-deethylase activity in the liver of both strains of rats. Michaelis-Menten analysis revealed no major difference between the strains. Phenacetin O-deethylase activity is inducible by both 3-methylcholanthrene and phenobarbitone in DA and Fischer rats. 3-Methylcholanthrene selectively increases the high-affinity component of activity, by 20- to 25-fold, whereas phenobarbitone selectively increases the low-affinity component, by two- to three-fold. It is concluded that there is no major difference between the DA and Fischer strains in their ability to O-deethylate phenacetin. Thus, unlike poor metabolizers of debrisoquine in the human population, who appear also to have impaired phenacetin O-deethylase activity, the DA rat is deficient in only the former activity.
D000818:Animals; D019388:Cytochrome P-450 CYP1A2; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013045:Species Specificity; D013347:Subcellular Fractions / Q000201:enzymology
D008748:Methylcholanthrene; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital