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大鼠非那西丁O-脱乙基酶活性:品系差异及酶诱导化合物的影响。

Phenacetin O-deethylase activity of the rat: strain differences and the effects of enzyme-inducing compounds.

作者信息

Kahn G C, Rubenfield M, Davies D S, Boobis A R

出版信息

Xenobiotica. 1987 Feb;17(2):179-87. doi: 10.3109/00498258709043927.

Abstract

Phenacetin O-deethylase activity in microsomal fractions from liver of DA and Fischer rats has been determined. No major sex or strain differences were found. Kinetic analysis revealed two major components of O-deethylase activity in the liver of both strains of rats. Michaelis-Menten analysis revealed no major difference between the strains. Phenacetin O-deethylase activity is inducible by both 3-methylcholanthrene and phenobarbitone in DA and Fischer rats. 3-Methylcholanthrene selectively increases the high-affinity component of activity, by 20- to 25-fold, whereas phenobarbitone selectively increases the low-affinity component, by two- to three-fold. It is concluded that there is no major difference between the DA and Fischer strains in their ability to O-deethylate phenacetin. Thus, unlike poor metabolizers of debrisoquine in the human population, who appear also to have impaired phenacetin O-deethylase activity, the DA rat is deficient in only the former activity.

摘要

已测定了DA大鼠和Fischer大鼠肝脏微粒体部分中对乙酰氨基酚O-脱乙基酶的活性。未发现明显的性别或品系差异。动力学分析表明,两种品系大鼠肝脏中的O-脱乙基酶活性有两个主要成分。米氏分析显示,两个品系之间没有明显差异。在DA大鼠和Fischer大鼠中,3-甲基胆蒽和苯巴比妥均可诱导对乙酰氨基酚O-脱乙基酶活性。3-甲基胆蒽选择性地使高亲和力成分的活性增加20至25倍,而苯巴比妥则选择性地使低亲和力成分的活性增加2至3倍。得出的结论是,DA大鼠和Fischer大鼠在对乙酰氨基酚O-脱乙基化能力方面没有明显差异。因此,与人群中异喹胍代谢不良者不同,后者似乎对乙酰氨基酚O-脱乙基酶活性也受损,而DA大鼠仅缺乏前者的活性。

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