DMD Celsis microsomes mean better data

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


     


Drug Metabolism and Disposition Fast Forward
First published on August 25, 2006; DOI: 10.1124/dmd.106.012005


This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.106.012005v1
34/12/2003    most recent
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 Jackson, J. P
Right arrow Articles by Goldstein, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jackson, J. P
Right arrow Articles by Goldstein, J. A.


Received for publication July 17, 2006.
Revised August 22, 2006.
Accepted for publication August 23, 2006.

Phenytoin Induction of the Cyp2c37 Gene is Mediated by the Constitutive Androstane Receptor

Jonathan P Jackson 1, Stephen S. Ferguson 1, Masahiko Negishi 1*, Joyce A. Goldstein 1

1 NIEHS

* Address correspondence to: E-mail: negishi{at}niehs.nih.gov

Abstract

The CYP2C subfamily of cytochrome P450 monoxygenases is responsible for the metabolism of approximately 20% of therapeutic drugs and many endogenous compounds in humans. These enzymes can be induced by prior treatment with drugs, resulting in changes in drug efficacy. Induction of human CYP2C enzymes by xenobiotics occurs at the transcriptional level and is reported to involve the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). In the present study, we report that murine CYP2C37 mRNA is induced by phenobarbital and phenytoin. In contrast, the mouse PXR (mPXR) agonist PCN did not induce CYP2C37 mRNA suggesting that PXR does not regulate this gene. The induction of CYP2C37 mRNA by phenobarbital and phenytoin is essentially abolished in CAR-null mice, thus induction of Cyp2c37 by these xenobiotics is CAR dependent. A functional CAR response element (CAR-RE) was identified at -2791 bp from the translation start site of the Cyp2c37 gene. Mutation of this CAR-RE abolished mouse CAR (mCAR) transactivation of a Cyp2c37 -2.9 kb luciferase reporter construct in HepG2 cells.


Key words: CAR, CYP induction, CYP2C, enzyme induction, PXR, transcriptional regulation, transgenic models


This article has been cited by other articles:


Home page
Drug Metab. Dispos.Home page
M. D. Merrell, J. P. Jackson, L. M. Augustine, C. D. Fisher, A. L. Slitt, J. M. Maher, W. Huang, D. D. Moore, Y. Zhang, C. D. Klaassen, et al.
The Nrf2 Activator Oltipraz Also Activates the Constitutive Androstane Receptor
Drug Metab. Dispos., August 1, 2008; 36(8): 1716 - 1721.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
R. A. B. van Waterschoot, A. E. van Herwaarden, J. S. Lagas, R. W. Sparidans, E. Wagenaar, C. M. M. van der Kruijssen, J. A. Goldstein, D. C. Zeldin, J. H. Beijnen, and A. H. Schinkel
Midazolam Metabolism in Cytochrome P450 3A Knockout Mice Can Be Attributed to Up-Regulated CYP2C Enzymes
Mol. Pharmacol., March 1, 2008; 73(3): 1029 - 1036.
[Abstract] [Full Text] [PDF]




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

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics.