Covalent binding of carbaryl (1-naphthyl-N-methyl-carbamate) to rat liver microsomes in vitro.
Enzyme mediated binding of carbaryl (1-naphthyl-N-methylcarbamate) to rat hepatic microsomes occurred in vitro in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen and was inhibited by nitrogen, carbon monoxide, reduced glutathione, cysteine, N-ethyl maleimide, and 2-diethylaminoethyl-2,2'-diphenylvalerate-HCl (SKF 525-A). Binding was markedly increased, 2- to 3-fold, by pretreatment of animals with phenobarbital or 3-methylcholanthrene and appeared to be dependent on the production of an active metabolite which was formed oxidatively in liver microsomes by cytochrome P-450 mixed-function oxidases. SDS-polyacrylamide disc gel electrophoresis of ether-extracted, solublized microsomes and the distribution of radioactivity after Pronase digestion, treatment with 1-fluoro-2,4-dinitrobenzene, and extraction with ethyl acetate and ether at pH 9 and 1 indicated that the radiolabeled products were covalently bound to amino acid residues of microsomal protein.
D000818:Animals; D012721:Carbaryl / Q000378:metabolism*; D004589:Electrophoresis, Disc; D066298:In Vitro Techniques; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011402:Pronase; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
D009249:NADP; D008748:Methylcholanthrene; D011402:Pronase; D012721:Carbaryl; D010634:Phenobarbital