Increased activity of androgen hydroxylases in liver microsomes of rats pretreated with phenobarbital and other drugs.

Increased activity of androgen hydroxylases in liver microsomes of rats pretreated with phenobarbital and other drugs.
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用苯巴比妥和其他药物预处理的大鼠肝微粒体中雄激素羟化酶的活性增加。

DOI:
10.1016/s0021-9258(18)81109-7
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发表时间:
1963
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
A. Klutch
A. Klutch
中科院分区:
--
文献类型:
--
作者:
A. Conney;A. Klutch

文献摘要

被引文献

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用苯巴比妥、苯丁氮酮和氯环利嗪等药物或多环烃如3-甲基胆蒽和3,4-苯并芘治疗大鼠,可使肝微粒体中还原的依赖三磷吡啶核苷酸的药物代谢酶的活性增加数倍(2-7)。酶活性的增加与完整动物中药物代谢的加速和药物作用时间的缩短是平行的。由于各种类固醇代谢酶在细胞内的分布和辅因子需求上与药物代谢酶相似,因此研究了给药对肝微粒体中类固醇代谢酶活性的影响。数据显示,用苯巴比妥或氯环利嗪治疗大鼠,可使肝微粒体中羟基化睾酮和Ad-雄烯-3,17-二酮的三磷吡啶核苷酸依赖酶系统的活性增加数倍。
Treatment of rats with drugs such as phenobarbital, phenylbutazone,’and chlorcyclizine or with polycyclic hydrocarbons such as 3-methylcholanthrene and 3, 4-benzpyrene stimulates several fold the activity of reduced triphosphopyridine nucleotide-dependent drug-metabolizing enzymes in liver microsomes (2-7). The increases in enzyme activity are paralleled by accelerated drug metabolism in the intact animal and by a shortened duration of drug action. Since various steroidmetabolizing enzymes resemble drug-metabolizing enzymes in their intracellular distribution and cofactor requirements, the effect of drug administration on the activity of steroid-metabolizing enzymes in liver microsomes was studied. Data are presented here that treatment of rats with phenobarbital or chlorcyclizine stimulates several fold the activity of triphosphopyridine nucleotide-dependent enzyme systems in liver microsomes that hydroxylate testosterone and Ad-androstene-3, 17-dione.