The content and activity of cytochrome P450 2E1 in liver microsomes from alcohol-preferring and non-preferring rats.
Constitutive levels of the ethanol-inducible cytochrome P450 (P450 2E1), as well as the extent of inducibility of this isozyme by pyrazole and 4-methylpyrazole in alcohol-preferring and non-preferring lines of rats, were investigated in order to evaluate whether the presence of this enzyme correlates with preference for ethanol. The content of P450 2E1 as detected immunochemically, as well as catalytic activity of P450 2E1 associated with the oxidation of preferred substrates such as dimethylnitrosamine and p-nitrophenol, was similar in liver microsomes from preferring and non-preferring rats. 4-Methylpyrazole was a poor inducer of P450 2E1 in both lines. Pyrazole treatment produced an identical 3- to 4-fold increase in content and catalytic activity of P450 2E1 in the two lines. The preferring and non-preferring rats do not appear to differ in their liver microsomal contents of cytochromes P450 2B1/B2 or 1A1. It appears that preference for ethanol is not associated with differences in the constitutive values or altered susceptibility to induction of P450 2E1 in the liver.
Winters
D K
DK
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029.
Cederbaum
A I
AI
D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D000077604:Fomepizole; D015151:Immunoblotting; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011720:Pyrazoles; C031280:pyrazole; D008748:Methylcholanthrene; D000077604:Fomepizole; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital