Stimulation of microsomal drug oxidation activities by incorporation into microsomes of purified NADPH-cytochrome c (P-450) reductase.

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概要

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• The effects of addition of purified NADPH-cytochrome <I>c</I> (P-450) reductase on microsomal activities of aniline hydroxylation, <I>p</I>-phenetidine 0-deethylation and ethylmorphine and aminopyrine N-dernethylations were investigated utilizing microsomes from untreated, phenobarbital-treated and 3-methylcholanthrene-treated rats. The purified reductase was incorporated into microsomes. The drug oxidation activities were increased by the fortification of microsomes with the reductase while the extent of increase in the activities varied with the substrate and microsomes employed. The most pronounced enhancement was seen in <I>p</I>-phenetidine 0-deethylation, followed by aniline hydroxylation and aminopyrine and ethylmorphine N-demethylations. The enhancement was more remarkable in microsomes from rats treated with 3-methylcholanthrene or phenobarbital. α-Naphthotlavone inhibited <I>p</I>-phenetidine 0-deethylation activity markedly when the reductase was incorporated into microsomes, indicating that a larger amount of a species of cytochrome P-450 sensitive to the inhibitor was capable of participating in the oxidation of this substrate in the presence of the added reductase. One of the two Km values seen with higher concentrations of aniline or aminopyrine was altered by the fortification of microsomes with the purified NADPH cytochrome <I>c</I> (P-450) reductase. From these results, we propose that NADPH-cytochrome <I>c</I> (P-450) reductase transfers electrons to the selected one or two of multiple species of cytochrome P-450 more preferentially depending upon the substrate and the concentration of the substrate in microsomal membranes.

• 公益社団法人 日本薬理学会の論文

著者

• Kubota Kikue

  Department Of Food Science And Nutrition Ochanomizu University

• Kamataki Tetsuya

  Department Of Biochemical Pharmacology Faculty Of Pharmaceutical Sciences Chiba University

• Kitada Mitsukazu

  Department Of Biochemical Pharmacology Faculty Of Pharmaceutical Sciences Chiba University

• Kitagawa Haruo

  Department Of Biochemical Pharmacology Faculty Of Pharmaceutical Sciences Chiba University

• KUBOTA Kikue

  Department of Biochemical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University

• KITAGAWA Haruo

  Department of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University

• KAMATAKI Tetsuya

  Department of Analytical Bio chemistry, School of Pharmacy, Hokkaido University

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