Hodgson A V, White T B, White J W, Strobel H W
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
Mol Cell Biochem. 1993 Mar 24;120(2):171-9. doi: 10.1007/BF00926090.
Metabolism of therapeutic drugs in the body by the mixed function oxidase system is an important consideration in the analysis of a drug's effectiveness. P450-dependent metabolism within the brain of a neuro-specific drug may affect the drug's course of action. To determine whether cytochrome P450 was expressed in brain, RNA was isolated from the whole brains of rats treated with a variety of known hepatic P450 inducers, including amitriptyline, imipramine, isosafrole, phenobarbital, and beta-naphthoflavone. The RNA was analyzed for the presence of P450 isozymes by the PCR technique. Differential expression of P450IA1, P450IIB1, P450IIB2, P450IID, and P450IIE1 was detected in the brain samples, depending on the treatment. Cytochrome P450 reductase expression was also detected in the brain samples, giving strong evidence that the brain contains a competent mixed function oxidase system under all conditions studied.
体内治疗药物通过混合功能氧化酶系统进行代谢,这在分析药物疗效时是一个重要的考虑因素。神经特异性药物在脑内的P450依赖性代谢可能会影响药物的作用过程。为了确定细胞色素P450是否在脑中表达,从用多种已知肝P450诱导剂(包括阿米替林、丙咪嗪、异黄樟素、苯巴比妥和β-萘黄酮)处理的大鼠全脑中分离RNA。通过PCR技术分析RNA中P450同工酶的存在情况。根据处理方式的不同,在脑样本中检测到了P450IA1、P450IIB1、P450IIB2、P450IID和P450IIE1的差异表达。在脑样本中也检测到了细胞色素P450还原酶的表达,这有力地证明了在所研究的所有条件下,脑内都含有一个有效的混合功能氧化酶系统。