AJP - GI AJP citation statistics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 285: G1335-G1344, 2003. First published July 31, 2003; doi:10.1152/ajpgi.00271.2003
0193-1857/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/6/G1335    most recent
00271.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
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 Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lou, H.
Right arrow Articles by Kaplowitz, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lou, H.
Right arrow Articles by Kaplowitz, N.

LIVER AND BILIARY TRACT

Chelerythrine stimulates GSH transport by rat Mrp2 (Abcc2) expressed in canine kidney cells

Huan Lou, Murad Ookhtens, Andrew Stolz, and Neil Kaplowitz

Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California 90033

Submitted 25 June 2003 ; accepted in final form 29 July 2003

Rat multidrug resistant protein 2 (Mrp2; Abcc2), an ATP-driven pump located on the canalicular domain of hepatocytes, exports glutathione S-conjugates (GS-X) and GSH among its wide variety of substrates. Previous studies have shown that chelerythrine (CHEL), a quaternary benzophenanthridine cation, reacts with GSH to form a reversible adduct under physiological conditions. Here we report that CHEL can strongly stimulate GSH efflux by Mrp2, when it is constitutively expressed in polarized canine kidney cells, thereby leading to the depletion of cellular GSH. Transepithelial transport experiments indicate that Mrp2 transports GSH and CHEL with a 1:1 stoichiometry, which can be readily inhibited by GS-bimane, a GS-X substrate for Mrp2. Moreover, CHEL can block Mrp2-mediated leukotriene C4 uptake by membrane vesicles with an IC50 {approx} 100 µM in the presence of GSH, but not S-methyl GSH or ophthalmic acid. Thus the thiol group of GSH is required for inhibition of Mrp2 in the presence of CHEL. Our results suggest that CHEL stimulates GSH efflux by forming a reversible GS-CHEL adduct, which is transported by Mrp2 and dissociates extracellularly.

glutathione conjugates; glutathione-chelerythrine adduct; membrane transport; membrane vesicles; polarized cells


Address for reprint requests and other correspondence: N. Kaplowitz, Keck School of Medicine, Univ. of Southern California, 2011 Zonal Ave., HMR101, Los Angeles, CA 90033 (E-mail: kaplowit{at}usc.edu).




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. Ito, T. Koresawa, K. Nakano, and T. Horie
Mrp2 is involved in benzylpenicillin-induced choleresis
Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G42 - G49.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.