Phenacetin O-deethylase activity of the rat: strain differences and the effects of enzyme-inducing compounds

Abstract

1. 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.

2. 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.

3. 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.

4. 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.