Potentiation of EPN-induced inhibition of liver microsomal carboxylesterase by addition of liver cytosol from 6-aminonicotinamide-treated, starved rats.

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  • SUGIYAMA Seiyu
    Laboratory of Biochemical Pharmacology and Biotoxicology. Faculty of Pharmaceutical Sciences, Chiba University
  • SATOH Tetsuo
    Laboratory of Biochemical Pharmacology and Biotoxicology. Faculty of Pharmaceutical Sciences, Chiba University
  • UENO Koichi
    Laboratory of Biochemical Pharmacology and Biotoxicology. Faculty of Pharmaceutical Sciences, Chiba University
  • IGARASHI Takashi
    Laboratory of Biochemical Pharmacology and Biotoxicology. Faculty of Pharmaceutical Sciences, Chiba University
  • KITAGAWA Haruo
    Laboratory of Biochemical Pharmacology and Biotoxicology. Faculty of Pharmaceutical Sciences, Chiba University

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  • Potentiation of EPN-induced Inhibition of Liver Microsomal Carboxylesterase by Addition of Liver Cytosol from 6-Aminonicotinam de-Treated, Starved Rats

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Addition of liver cytosol from 16 hr-starved rats treated with 6-aminonicotinamide to rat liver microsomes caused potentiation of the anti-carboxylesterase action of ethyl-p-nitrophenyl phenylphosphonothioate (EPN). This was not found when liver cytosol from non-pretreated rats after 16 hr-starvation was used. This potentiation of EPN-induced inhibition of carboxylesterase may be, at least in part, explained by the fact that treatment of rats with 6-aminonicotinamide resulted in a significant increase in NADPH level in liver cytosol which, in turn, stimulated formation of an EPN oxygen analog, a potent inhibitor of carboxylesterase, through cytochrome P-450-coupled monooxygenase.

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