Home LiteratureArticle Details
PMID: 8487757 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction.

Molecular and cellular biochemistry ·Vol. 120 ·No. 2 ·1993-03-24 ·Pages 171-9

Hodgson AV, White TB, White JW, Strobel HW

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
References (23)
23 references, click to expand
  1. Immunohistochemical localization of cytochrome P-450 in rat brain.
    Neuroscience. 1987 Mar;20(3):829-33 PMID: 3299136
  2. On the occurrence of cytochrome P-450 and aryl hydrocarbon hydroxylase activity in rat brain.
    J Exp Med. 1977 Jun 1;145(6):1607-11 PMID: 194012
  3. Cytochrome P-450 and NADPH cytochrome c reductase in rat brain: formation of catechols and reactive catechol metabolites.
    Biochem Biophys Res Commun. 1977 Oct 10;78(3):919-26 PMID: 410418
  4. MPTP, the neurotoxin inducing Parkinson's disease, is a potent competitive inhibitor of human and rat cytochrome P450 isozymes (P450bufI, P450db1) catalyzing debrisoquine 4-hydroxylation.
    Biochem Biophys Res Commun. 1987 Nov 13;148(3):1144-50 PMID: 3500719
  5. Cytochrome P-450 b and c in the rat brain and pituitary gland.
    Mol Pharmacol. 1988 Jan;33(1):31-7 PMID: 3275864
  6. Preparation and properties of highly purified cytochrome p-450 and NADPH-cytochrome P-450 reductase from pulmonary microsomes of untreated rabbits.
    Mol Pharmacol. 1977 Sep;13(5):911-23 PMID: 408601
  7. The Ah locus: biochemical basis for genetic differences in brain tumor formation in mice.
    Genetics. 1979 Aug;92(4):1205-10 PMID: 520822
  8. Immunohistochemical localization of cytochrome P-450 in the rat brain.
    Neurosci Lett. 1988 Jan 22;84(2):109-14 PMID: 3340317
  9. Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum.
    Adv Pharmacol. 1966;4:219-61 PMID: 5333769
  10. Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system.
    Neuroscience. 1990;34(2):451-63 PMID: 2333153
  11. Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6.
    Mol Pharmacol. 1991 Jul;40(1):63-8 PMID: 1857341
  12. Reconstitution of the brain mixed function oxidase system: purification of NADPH-cytochrome P450 reductase and partial purification of cytochrome P450 from whole rat brain.
    J Neurochem. 1992 Aug;59(2):575-81 PMID: 1629729
  13. Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine.
    Lancet. 1985 Nov 30;2(8466):1213-6 PMID: 2866293
  14. Cytochrome reductase activities in rat brain microsomes during development.
    J Neurochem. 1982 Oct;39(4):1047-9 PMID: 7119779
  15. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  16. First-strand cDNA synthesis primed with oligo(dT).
    Methods Enzymol. 1987;152:316-25 PMID: 2443800
  17. Phosphatidylcholine requirement in the enzymatic reduction of hemoprotein P-450 and in fatty acid, hydrocarbon, and drug hydroxylation.
    J Biol Chem. 1970 Sep 25;245(18):4851-4 PMID: 4393962
  18. Amplification and analysis of DNA sequences in single human sperm and diploid cells.
    Nature. 1988 Sep 29;335(6189):414-7 PMID: 3419517
  19. Xenobiotic metabolism in human brain--presence of cytochrome P-450 and associated mono-oxygenases.
    Brain Res. 1989 Sep 4;496(1-2):331-5 PMID: 2804643
  20. The drug and carcinogen metabolism system of rat colon microsomes.
    Arch Biochem Biophys. 1978 Feb;186(1):128-38 PMID: 629529
  21. Pharmacological implications of microsomal enzyme induction.
    Pharmacol Rev. 1967 Sep;19(3):317-66 PMID: 4383307
  22. Parkinson's disease and cytochrome P450: a possible link?
    Med Hypotheses. 1990 Aug;32(4):277-82 PMID: 2233418
  23. Regional distribution of cytochrome P-450 in the rat brain: spectral quantitation and contribution of P-450b,e, and P-450c,d.
    J Neurochem. 1988 Apr;50(4):1057-65 PMID: 3258014
Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
Published
1993-03-24
Pages
171-9
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
Grants
NIMH NIH HHS · MH44923 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com