Effects of anti-NADPH-cytochrome c reductase and anti-cytochrome b5 antibodies on the hepatic and pulmonary microsomal metabolism and covalent binding of the pulmonary toxin 4-ipomeanol. |
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Authors: | H A Sasame J R Gillette M R Boyd |
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Institution: | Laboratory of Chemical Pharmacology National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland 20014 USA;Clinical Pharmacology Branch National Cancer Institute National Institutes of Health Bethesda, Maryland 20014 USA |
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Abstract: | An antibody prepared against purified rat liver NADPH-cytochrome reductase inhibited both the pulmonary and hepatic microsomal covalent binding of 4-ipomeanol as well as the respective NADPH-cytochrome reductase activities, findings which are consistent with previous studies which indicated the participation of cytochrome P450 in the metabolic activation of the toxin. An antibody prepared against purified rat liver cytochrome b5, which strongly inhibited both the rat hepatic and pulmonary NADH-dependent cytochrome reductases, and was inactive against the respective NADPH-dependent cytochrome reductases, had little effect on metabolic activation of 4-ipomeanol by hepatic microsomes, but strongly inhibited both the NADH-supported and the NADPH-supported pulmonary microsomal metabolism and covalent binding of the compound. These results suggest that metabolic activation of 4-ipomeanol involves a two-electron transfer in which transfer of the second electron via cytochrome b5 is rate-limiting in lung microsomes. |
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Keywords: | Address inquiries and requests for reprints to Dr M Boyd Rm 6N-105 Bldg 10 NIH Bethesda Maryland 20014 |
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