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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Cytochromes P450 and Flavin Monooxygenases—Targets and Sources of Nitric Oxide
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- 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.)
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