Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction.
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.
Hodgson
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AV
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225.
White
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TB
White
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JW
Strobel
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HW
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001571:Benzoflavones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007099:Imipramine / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010634:Phenobarbital / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism; D012451:Safrole / Q000494:pharmacology; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000639:Amitriptyline; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D007099:Imipramine; D012451:Safrole; C015959:isosafrole; D010634:Phenobarbital