Influence of sex and inducer treatment on the high- and low-affinity forms of hepatic microsomal erythromycin N-demethylase in rats.
To study the regulation of the multiple forms of erythromycin N-demethylase, we determined the influence of sex and inducer treatment on this mixed-function oxidase activity in adult Wistar rats injected intraperitoneally once daily for 4 days with dexamethasone, pregnenolone-16 alpha-carbonitrile, phenobarbital, or 2% Tween 80 (control). Based on the results from a computer curve-fitting procedure (ENZFITTER) as well as Eadie-Hofstee and Lineweaver-Burk plots, at least two forms of erythromycin N-demethylase were present in control, dexamethasone, pregnenolone-16 alpha-carbonitrile, and phenobarbital-treated male rats and in control and dexamethasone-treated female rats. Only a high-affinity form was apparent in pregnenolone-16 alpha-carbonitrile and phenobarbital-treated female rats. Therefore, more than one form of erythromycin N-demethylase exists in hepatic microsomes from adult rats, depending on sex and inducer treatment. As well, at a substrate concentration commonly used in the erythromycin N-demethylase assay, the relative contribution of the high- and low-affinity forms to the enzyme activity varies with sex and inducer treatment.
Chang
T
T
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Levine
M
M
Bellward
G D
GD
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000737:chemistry; D010634:Phenobarbital / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D011285:Pregnenolone Carbonitrile; D004917:Erythromycin; D003907:Dexamethasone; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital