Abstract
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.
MeSH Terms
Amitriptyline/pharmacology
Animals
Base Sequence
Benzoflavones/pharmacology
Brain/drug effects,enzymology
Cytochrome P-450 Enzyme System/biosynthesis,genetics
Enzyme Induction/drug effects
Female
Imipramine/pharmacology
Isoenzymes/biosynthesis,genetics
Male
Mixed Function Oxygenases/biosynthesis,genetics
Molecular Sequence Data
Nerve Tissue Proteins/biosynthesis,genetics
Phenobarbital/pharmacology
Polymerase Chain Reaction
RNA, Messenger/biosynthesis
Rats
Rats, Sprague-Dawley/metabolism
Safrole/pharmacology
beta-Naphthoflavone
Chemicals
Benzoflavones
Isoenzymes
Nerve Tissue Proteins
RNA, Messenger
Amitriptyline
beta-Naphthoflavone
Cytochrome P-450 Enzyme System
Mixed Function Oxygenases
Imipramine
Safrole
isosafrole
Phenobarbital
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hodgson A V
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
White T B
White J W
Strobel H W
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