患有高胆红素尿症的大鼠突变株肝脏微粒体中细胞色素P - 450特定形式的减少。

Decrease in the specific forms of cytochrome P-450 in liver microsomes of a mutant strain of rat with hyperbilirubinuria.

作者信息

Ohmori S, Kuriya S, Uesugi T, Horie T, Sagami F, Mikami T, Kawaguchi A, Rikihisa T, Kanakubo Y

机构信息

Faculty of Pharmaceutical Sciences, Chiba University, Japan.

出版信息

Res Commun Chem Pathol Pharmacol. 1991 May;72(2):243-53.

PMID:1876754

Abstract

Eisai-hyperbilirubinuria rats (EHBR) is a mutant originated from Sprague Dawley rats. The activities of UDP-glucuronyltransferase and drug metabolizing enzymes in EHBR were compared with those in Sprague Dawley rats as the control. The activity of aniline hydroxylase was significantly increased in liver microsomes of EHBR whereas the activity of ethylmorphine N-demethylase was found to be significantly decreased in EHBR as compared to control rats. In addition, the activity of testosterone 7 alpha-hydroxylase was increased in EHBR whereas the activity of testosterone 6 beta-hydroxylase was significantly decreased in EHBR as compared to control rats. Western blot analysis of liver microsomes of EHBR with antibodies to P-450IA2, P-450IIB1, P-450IIC11 and P-450IIIA2 showed that the amounts of P-450IIB1 and P-450IIIA2 in liver microsomes were significantly lower in EHBR than in control rats. These results indicated the form-specific alteration in the amounts of cytochrome P-450 in liver microsomes of EHBR.

摘要

卫材高胆红素尿大鼠（EHBR）是一种源自斯普拉格-道利大鼠的突变体。将EHBR中尿苷二磷酸葡萄糖醛酸基转移酶和药物代谢酶的活性与作为对照的斯普拉格-道利大鼠的活性进行比较。与对照大鼠相比，EHBR肝微粒体中苯胺羟化酶的活性显著增加，而EHBR中N-脱甲基乙基吗啡的活性显著降低。此外，与对照大鼠相比，EHBR中睾酮7α-羟化酶的活性增加，而EHBR中睾酮6β-羟化酶的活性显著降低。用针对P-450IA2、P-450IIB1、P-450IIC11和P-450IIIA2的抗体对EHBR肝微粒体进行蛋白质印迹分析表明，EHBR肝微粒体中P-450IIB1和P-450IIIA2的量显著低于对照大鼠。这些结果表明EHBR肝微粒体细胞色素P-450含量存在形式特异性改变。