| 2900731 |
Shigenaga MK, Trevor AJ, Castagnoli N Jr: Metabolism-dependent covalent binding of (S)-[5-3H] nicotine to liver and lung microsomal macromolecules. Drug Metab Dispos. 1988 May-Jun;16(3):397-402.
Incubation of (S)-[5-3H] nicotine with rabbit liver microsomes in the presence of dioxygen and NADPH results in the formation of metabolites that bind covalently to microsomal macromolecules (250-550 pmol/mg of protein/hr). The partition ratio [(S)-nicotine metabolized/(S)-nicotine equivalents covalently bound] ranged between 250:1 and 500:1. The addition of SKF 525-A, cytochrome c, or n-octylamine inhibited both (S)-nicotine metabolism and covalent binding whereas phenobarbital pretreatment increased the rates of metabolism and covalent binding. Sodium cyanide, which forms stable adducts with the cytochrome P-450-generated iminium ion metabolites of (S)-nicotine and a variety of other tertiary amines, inhibited covalent binding but also decreased the rate of (S)-nicotine metabolism. The metabolism-dependent covalent binding of (S)-nicotine and its conversion to the delta 1',5'-iminium species were observed also in microsomal incubations prepared from rabbit lung and human liver tissues. |
31(0,1,1,1) |