JPET Introducing ALZET?ew Model 2006 Pump

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


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on February 8, 2006; DOI: 10.1124/jpet.105.093765

This Article
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
jpet.105.093765v1
317/2/537    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 Moffit, J. S
Right arrow Articles by Manautou, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moffit, J. S
Right arrow Articles by Manautou, J.


Received for publication August 4, 2005.
Revised February 6, 2006.
Accepted for publication February 6, 2006.

Induction of hepatic transporters Mrp3 and Mrp4 by clofibrate is regulated by PPAR{alpha}

Jeffrey S Moffit 1, Lauren M Aleksunes 1, Jonathan M Maher 2, George L Scheffer 3, Curtis D Klaassen 2, Jose Manautou 1*

1 University of Connecticut 2 University of Kansas 3 VU Medical Center, Amsterdam

* Address correspondence to: E-mail: jose.manautou{at}uconn.edu

Abstract

Hepatic transporters play a vital role in the disposition of endogenous compounds and xenobiotics in the liver. The current study investigates the expression and regulation of hepatic efflux transporters in response to treatment with the PPAR{alpha} agonist clofibrate (CFB). Changes in mRNA and protein levels for several hepatic transporters were assessed in male CD-1 mice after 10 days of CFB dosing (500mg/kg, i.p.). Administration of CFB up-regulated mRNA levels for breast cancer resistance protein (Bcrp) and multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4, respectively). Western blot analysis confirmed that CFB enhances protein expression of liver Bcrp, Mrp3, and Mrp4 in CD-1 mice. To further characterize the regulation of these hepatic transporters, CFB-mediated changes in transporter gene expression were assessed in wild-type (sv/129) and PPAR{alpha}-null male mice. Wild-type mice treated with CFB showed similar changes in mRNA levels for all of these transporters, whereas the PPAR{alpha}-null mice did not. Although, protein expression of Mrp3 and Mrp4 in the wild-type mice correlated well with changes in mRNA levels, Bcrp protein was not up-regulated by CFB treatment. These results show that PPAR{alpha} activation by CFB coordinately regulates the hepatic efflux transporters Mrp3 and Mrp4. Induction of Mrp3 and Mrp4 by CFB may alter the disposition of toxicants and xenobiotics that are substrates for these transporters.


Key words: Mrp3, Mrp4, PPAR-alpha, clofibrate, liver, transporters


This article has been cited by other articles:


Home page
 Toxicol SciHome page
J. M. Maher, L. M. Aleksunes, M. Z. Dieter, Y. Tanaka, J. M. Peters, J. E. Manautou, and C. D. Klaassen
Nrf2- and PPAR{alpha}-Mediated Regulation of Hepatic Mrp Transporters after Exposure to Perfluorooctanoic Acid and Perfluorodecanoic Acid
Toxicol. Sci., December 1, 2008; 106(2): 319 - 328.
[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.