细胞色素P450系统参与α-（溴异戊酰基）脲的微粒体脱溴作用。

Involvement of a cytochrome P450 system in microsomal debromination of alpha-(bromisovaleryl)urea.

作者信息

Oka K, Kitamura S, Tatsumi K

机构信息

Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.

出版信息

J Pharm Pharmacol. 1996 Sep;48(9):930-2. doi: 10.1111/j.2042-7158.1996.tb06004.x.

DOI:10.1111/j.2042-7158.1996.tb06004.x

PMID:8910855

Abstract

The reductive debromination of a hypnotic, (alpha-bromisovaleryl)urea to (3-methylbutyryl)urea by rat liver microsomes was studied. Pretreatment of rats with cytochrome P450 inducers such as phenobarbitone, 3-methylcholanthrene, acetone and pregnenolone-16 alpha-carbonitrile enhanced the debromination of (alpha-bromisovaleryl)urea by liver microsomes. Microsomal debromination was inhibited by cytochrome P450 inhibitors such as metyrapone, alpha-naphthoflavone, SKF 525-A and carbon monoxide. Microsomal debromination was enhanced by addition of NADPH-cytochrome P450 reductase and inhibited by addition of an antibody against the flavo enzyme to the liver microsomes. A reconstituted cytochrome P450 system containing NADPH-cytochrome P450 reductase, and cytochrome P450 1AI or P450 2BI exhibited debrominating activity toward the hypnotic. These results indicated that a cytochrome P450 system plays an essential role in the microsomal debromination of (alpha-bromisovaleryl)urea.

摘要

研究了大鼠肝微粒体将催眠药（α-溴异戊酰基）脲还原脱溴生成（3-甲基丁酰基）脲的过程。用细胞色素P450诱导剂如苯巴比妥、3-甲基胆蒽、丙酮和孕烯醇酮-16α-腈预处理大鼠，可增强肝微粒体对（α-溴异戊酰基）脲的脱溴作用。微粒体脱溴作用受到细胞色素P450抑制剂如甲吡酮、α-萘黄酮、SKF 525-A和一氧化碳的抑制。添加NADPH-细胞色素P450还原酶可增强微粒体脱溴作用，而向肝微粒体中添加针对黄素酶的抗体则可抑制该作用。含有NADPH-细胞色素P450还原酶以及细胞色素P450 1AI或P450 2BI的重组细胞色素P450系统对该催眠药表现出脱溴活性。这些结果表明，细胞色素P450系统在（α-溴异戊酰基）脲的微粒体脱溴过程中起重要作用。