Hepatic microsomal induction in rat liver: heterogeneity of response.
The concept that urinary 6-hydroxycortisol excretion patterns reflect all microsomal enzyme activities remains a subject of controversy. Three different microsomal hydroxylase activities were therefore studied in rat liver after the animals were intoxicated with alcohol, phenobarbital, or a combination thereof. The activities of pentobarbital hydroxylase, aniline hydroxylase, and cortisol 6-hydroxylase (the enzyme metabolizing cortisol to 6-hydroxycortisol) were assayed simultaneously after each treatment. A heterogeneity of enzyme activities was noted. Cortisol 6-hydroxylase activity did not parallel the activity patterns of the two other hydroxylases. The data suggest that before urinary 6-hydroxycortisol excretion patterns can be utilized as an index of microsomal enzyme induction, the effect of the specific drug on individual cytochrome P-450 hydroxylases is required.
D000815:Aniline Hydroxylase / Q000096:biosynthesis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010424:Pentobarbital / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013250:Steroid Hydroxylases
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D000815:Aniline Hydroxylase; C022657:steroid hormone 6-beta-hydroxylase; C022327:pentobarbital hydroxylase; D010424:Pentobarbital; D010634:Phenobarbital