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Meeting ReportSymposium Report

Cytochromes P450 and Flavin Monooxygenases—Targets and Sources of Nitric Oxide

Edward T. Morgan, Volker Ullrich, Andreas Daiber, Patrick Schmidt, Naoki Takaya, Hirofumi Shoun, John C. McGiff, Adebayo Oyekan, Craig J. Hanke, William B. Campbell, Chang-Shin Park, Ju-Seop Kang, Hyeon-Gyu Yi, Young-Nam Cha, Daniel Mansuy and Jean-Luc Boucher
Drug Metabolism and Disposition November 2001, 29 (11) 1366-1376;
Edward T. Morgan
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Volker Ullrich
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Andreas Daiber
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Patrick Schmidt
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Naoki Takaya
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Hirofumi Shoun
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John C. McGiff
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Adebayo Oyekan
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Craig J. Hanke
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William B. Campbell
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Chang-Shin Park
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Ju-Seop Kang
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Hyeon-Gyu Yi
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Young-Nam Cha
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Daniel Mansuy
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Jean-Luc Boucher
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Abstract

This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 01 meeting in Orlando, FL. The presentations addressed the mechanisms of inhibition and regulation of cytochrome P450 and flavin monooxygenase enzymes by nitric oxide. They also highlighted the consequences of these effects on metabolism of drugs and volatile amines as well as on important physiological parameters, such as control of blood pressure, renal ion transport, and steroidogenesis. This is achieved via regulation of P450-dependent prostacyclin, hydroxyeicosatetraenoic acid, and epoxyeicosatrienoic acid formation. Conversely, the mechanisms and relative importance of nitric oxide synthases and P450 enzymes in NO production from endogenous and synthetic substrates were also addressed.

Footnotes

  • This work was supported in part by United States Public Health Service Grants GM53093 (E.T.M.), HL34300 and HL25394 (J.C.M.), HL59884 (A.O.), and HL52159 and DK58145 (W.B.C.); by UH1 03674 and an Established Investigator Award (0040119N) from the American Heart Association (A.O.); and by the Deutsche Forschungsgemeinschaft Schwerpunktprogramm “Radikale in der enzymatischen Katalyse” and the Fonds der Chemischen Industrie (V.U.).

  • Abbreviations used are::
    NOS
    nitric oxide synthase
    P450
    cytochrome P450
    iNOS
    inducible NOS
    LPS
    bacterial lipopolysaccharide
    PB
    phenobarbital
    PN
    peroxynitrite
    SOD
    superoxide dismutase
    PGI2
    prostacyclin
    SIN-1
    3-morpholinosydnonimine N-ethylcarbamide
    3-NT
    3-nitrotyrosine
    CPO
    chloroperoxidase
    AA
    arachidonic acid
    HETE
    hydroxyeicosatetraenoic acid
    l-NAME
    l-nitroarginine methyl ester
    GFR
    glomerular filtration rate
    UV
    urine volume
    UNaV
    urinary sodium excretion
    DBDD
    12,12-dibromododec-11-enoic acid
    PT
    proximal tubules
    ET-1
    endothelin-1
    nNOS
    neuronal NOS
    SNP
    sodium nitroprusside
    ZG
    zona glomerulosa
    AII
    angiotensin II
    DETA nonoate
    (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate
    AdeNOS
    adenovirus encoding endothelial NOS
    FMO
    flavin-containing monooxygenase
    TMAU
    trimethylaminuria
    TMA
    trimethylamine
    TMAO
    trimethylamineN-oxide
    CVH
    chronic viral hepatitis
    RA
    ranitidine
    RANO
    ranitidine N-oxide
    SNAP
    S-nitroso-N-acetylpenicillamine
    BHA
    butylated hydroxyanisole
    DTT
    dithiothreitol
    NOHA
    Nω-hydroxyarginine
    BH4
    tetrahydrobiopterin
    homo-NOHA
    Nω-hydroxyhomo-l-arginine
    nor-NOHA
    Nω-hydroxynor-l-arginine
    dinor-NOHA
    Nω-hydroxydinor-l-arginine
    • Received June 21, 2001.
    • Accepted August 6, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 29 (11)
Drug Metabolism and Disposition
Vol. 29, Issue 11
1 Nov 2001
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Meeting ReportSymposium Report

Cytochromes P450 and Flavin Monooxygenases—Targets and Sources of Nitric Oxide

Edward T. Morgan, Volker Ullrich, Andreas Daiber, Patrick Schmidt, Naoki Takaya, Hirofumi Shoun, John C. McGiff, Adebayo Oyekan, Craig J. Hanke, William B. Campbell, Chang-Shin Park, Ju-Seop Kang, Hyeon-Gyu Yi, Young-Nam Cha, Daniel Mansuy and Jean-Luc Boucher
Drug Metabolism and Disposition November 1, 2001, 29 (11) 1366-1376;

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Meeting ReportSymposium Report

Cytochromes P450 and Flavin Monooxygenases—Targets and Sources of Nitric Oxide

Edward T. Morgan, Volker Ullrich, Andreas Daiber, Patrick Schmidt, Naoki Takaya, Hirofumi Shoun, John C. McGiff, Adebayo Oyekan, Craig J. Hanke, William B. Campbell, Chang-Shin Park, Ju-Seop Kang, Hyeon-Gyu Yi, Young-Nam Cha, Daniel Mansuy and Jean-Luc Boucher
Drug Metabolism and Disposition November 1, 2001, 29 (11) 1366-1376;
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  • Article
    • Abstract
    • Isoform-Selective Role of NO in Hepatic Cytochrome P450 Down-Regulation (E.T.M.)
    • Reactions of P450 Proteins with Peroxynitrite (V.U., A.D., P.S., T.N., and H.S.)
    • NO Exerts a Tonic Inhibitory Effect on 20-HETE Formation: Renal Functional Implications (J.C.McG. and A.O.)
    • Nitric Oxide Inhibits Steroid Hormone Synthesis in Adrenal Zona Glomerulosa Cells (C.J.H. and W.B.C.)
    • Overproduction of Nitric Oxide Causes Reduction of Hepatic Flavin-Containing Monooxygenase (FMO) Activity and Trimethylaminuria in Patients with Chronic Viral Hepatitis (C.S.P, J.S.K., H.G.Y., and Y.N.C.)
    • Formation of Nitric Oxide by Cytochromes P450: Comparison with NO Synthases (D.M. and J.-L. B.)
    • Acknowledgments
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