MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ferrari, L.
Right arrow Articles by Morgan, E. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferrari, L.
Right arrow Articles by Morgan, E. T.

Vol. 60, Issue 1, 209-216, July 2001

Role of Nitric Oxide in Down-Regulation of CYP2B1 Protein, but Not RNA, in Primary Cultures of Rat Hepatocytes

Luc Ferrari, Ning Peng, James R. Halpert, and Edward T. Morgan

Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia (L.F., N.P., E.T.M.); Centre du Médicament, Institut National de la Santé et de la Recherche Médicale U525, Faculty of Pharmacy of Nancy, Nancy, France (L.F.); and Department of Pharmacology and Toxicology, University of Texas Medical Branch at Galveston, Galveston, Texas (J.R.H.)

There are conflicting reports about the role of nitric oxide in the down-regulation of cytochrome P450 that occurs when animals or cultured hepatocytes are exposed to inflammatory stimuli. Here, we investigated the participation of NO in the down-regulation of CYP2B1 by bacterial endotoxin (LPS) in rat hepatocytes cultured on Matrigel. LPS caused the down-regulation of CYP2B1 mRNA to 20% of control values within 12 h of treatment, and this was not reversed by concentrations of NO synthase inhibitors that completely blocked NO production. LPS was several orders of magnitude more potent in the down-regulation of CYP2B1 mRNA than in induction of NO production. In contrast, concentrations of LPS in the 1 to 100 ng/ml range induced NO production and produced a rapid down-regulation of CYP2B1 protein to 30% and <5% of control at 6 and 24 h, respectively, that could be completely prevented both by inhibitors of NO synthase and by LY83583, which prevents NO synthase-2 induction. The blockade of CYP2B1 down-regulation by NO synthase inhibitors was reversed by arginine, and the NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine mimicked CYP2B1 protein suppression. Taken together, these experiments demonstrate two independent mechanisms of CYP2B1 down-regulation by LPS: a rapid, NO-dependent suppression of the protein occurring at high concentrations of LPS and a slower, NO-independent pretranslational suppression occurring at low concentrations of LPS.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
E. T. Morgan, K. B. Goralski, M. Piquette-Miller, K. W. Renton, G. R. Robertson, M. R. Chaluvadi, K. A. Charles, S. J. Clarke, M. Kacevska, C. Liddle, et al.
Regulation of Drug-Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer
Drug Metab. Dispos., February 1, 2008; 36(2): 205 - 216.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C.-M. Lee, B.-Y. Kim, L. Li, and E. T. Morgan
Nitric Oxide-dependent Proteasomal Degradation of Cytochrome P450 2B Proteins
J. Biol. Chem., January 11, 2008; 283(2): 889 - 898.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
O. Kourylko, C. Fradette, M. Arcand, and P. du Souich
MODULATION OF CYP1A2 AND CYP3A6 CATALYTIC ACTIVITIES BY SERUM FROM RABBITS WITH A TURPENTINE-INDUCED INFLAMMATORY REACTION AND INTERLEUKIN 6
Drug Metab. Dispos., January 1, 2006; 34(1): 27 - 35.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
R. Vuppugalla and R. Mehvar
SHORT-TERM INHIBITORY EFFECTS OF NITRIC OXIDE ON CYTOCHROME P450-MEDIATED DRUG METABOLISM: TIME DEPENDENCY AND REVERSIBILITY PROFILES IN ISOLATED PERFUSED RAT LIVERS
Drug Metab. Dispos., December 1, 2004; 32(12): 1446 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Yaghi, J. R. Bend, C. D. Webb, D. C. Zeldin, S. Weicker, S. Mehta, and D. G. McCormack
Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia
Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1260 - L1267.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. S. Riddick, C. Lee, A. Bhathena, Y. E. Timsit, P.-Y. Cheng, E. T. Morgan, R. A. Prough, S. L. Ripp, K. K. M. Miller, A. Jahan, et al.
TRANSCRIPTIONAL SUPPRESSION OF CYTOCHROME P450 GENES BY ENDOGENOUS AND EXOGENOUS CHEMICALS
Drug Metab. Dispos., April 1, 2004; 32(4): 367 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
E. T. Morgan, V. Ullrich, A. Daiber, P. Schmidt, N. Takaya, H. Shoun, J. C. McGiff, A. Oyekan, C. J. Hanke, W. B. Campbell, et al.
Cytochromes P450 and Flavin Monooxygenases---Targets and Sources of Nitric Oxide
Drug Metab. Dispos., November 1, 2001; 29(11): 1366 - 1376.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics