![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 59, Issue 5, 974-980, May 2001
Laboratory of Experimental Hepatology, Department of
Gastroenterology (C.G.D., D.R.W., R.O., R.P.J.O.) and Surgical
Laboratory, Department of Surgery (I.G.S.), Academic Medical Center,
Amsterdam, The Netherlands
MRP2 is an apical transporter expressed in hepatocytes and the
epithelial cells of the small intestine and kidney proximal tubule. It
extrudes organic anions, conjugated compounds, and some uncharged
amphipaths. We studied the transport of an abundant food-derived
carcinogen,
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
in vitro, using an MRP2 transfected epithelial cell line (MDCK II) and intestinal explants from Wistar and MRP2-deficient TR
rats in Ussing chambers. In the experiments with the
transfected cell line, we could demonstrate more than 3-fold higher
transport from basolateral to apical than vice versa, whereas the
transport in the parent cell line was equal in both directions. These
results were confirmed in studies using isolated pieces of small
intestine from Wistar and TR rats in the Ussing chamber.
Subsequent in vivo experiments demonstrated that after oral
administration, absorption of PhIP was 2-fold higher in the
TR rat than in the Wistar rat. Consequently, PhIP tissue
levels in several organs (liver, kidney, lung, and colon) were 1.7- to 4-fold higher 48 h after oral administration. MRP2 mediated
transport of unchanged PhIP probably involves intracellular GSH,
because GSH depletion by BSO-treatment in Wistar rats reduced
intestinal secretion in the Ussing chamber to the same level as in
TR rats. In accordance, BSO treatment increased oral
bioavailability in intact Wistar rats. This study shows for the first
time that MRP2-mediated extrusion reduces oral bioavailability of a
xenobiotic and protects against an abundant food-derived carcinogen.
This article has been cited by other articles:
|
|
 |
|
  J. S. Lagas, R. W. Sparidans, R. A. B. van Waterschoot, E. Wagenaar, J. H. Beijnen, and A. H. Schinkel P-Glycoprotein Limits Oral Availability, Brain Penetration, and Toxicity of an Anionic Drug, the Antibiotic Salinomycin Antimicrob. Agents Chemother., March 1, 2008; 52(3): 1034 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. H. Vlaming, K. Mohrmann, E. Wagenaar, D. R. de Waart, R. P. J. O. Elferink, J. S. Lagas, O. van Tellingen, L. D. Vainchtein, H. Rosing, J. H. Beijnen, et al. Carcinogen and Anticancer Drug Transport by Mrp2 in Vivo: Studies Using Mrp2 (Abcc2) Knockout Mice J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Johnson, P. Zhang, J. D. Schuetz, and K. L. R. Brouwer CHARACTERIZATION OF TRANSPORT PROTEIN EXPRESSION IN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) 2-DEFICIENT RATS Drug Metab. Dispos., April 1, 2006; 34(4): 556 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Merino, J. W. Jonker, E. Wagenaar, A. E. van Herwaarden, and A. H. Schinkel The Breast Cancer Resistance Protein (BCRP/ABCG2) Affects Pharmacokinetics, Hepatobiliary Excretion, and Milk Secretion of the Antibiotic Nitrofurantoin Mol. Pharmacol., May 1, 2005; 67(5): 1758 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C G Dietrich, A Geier, H E Wasmuth, S Matern, C Gartung, D R de Waart, and R P J O Elferink Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen Gut, December 1, 2004; 53(12): 1850 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shoji, H. Suzuki, H. Kusuhara, Y. Watanabe, S. Sakamoto, and Y. Sugiyama ATP-dependent transport of organic anions into isolated basolateral membrane vesicles from rat intestine Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G749 - G756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C G Dietrich, A Geier, and R P J Oude Elferink ABC of oral bioavailability: transporters as gatekeepers in the gut Gut, December 1, 2003; 52(12): 1788 - 1795. [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. van Herwaarden, J. W. Jonker, E. Wagenaar, R. F. Brinkhuis, J. H. M. Schellens, J. H. Beijnen, and A. H. Schinkel The Breast Cancer Resistance Protein (Bcrp1/Abcg2) Restricts Exposure to the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Cancer Res., October 1, 2003; 63(19): 6447 - 6452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mochida, K.-i. Taguchi, S. Taniguchi, M. Tsuneyoshi, H. Kuwano, T. Tsuzuki, M. Kuwano, and M. Wada The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in ApcMin/+ mice Carcinogenesis, July 1, 2003; 24(7): 1219 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R O. Elferink Cholestasis Gut, May 1, 2003; 52(90002): ii42 - 48. [Abstract] [Full Text]
|
|
|
|
|
|
P. M. Gerk and M. Vore Regulation of Expression of the Multidrug Resistance-Associated Protein 2 (MRP2) and Its Role in Drug Disposition J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Ito, C. J. Oleschuk, C. Westlake, M. Z. Vasa, R. G. Deeley, and S. P. C. Cole Mutation of Trp1254 in the Multispecific Organic Anion Transporter, Multidrug Resistance Protein 2 (MRP2) (ABCC2), Alters Substrate Specificity and Results in Loss of Methotrexate Transport Activity J. Biol. Chem., October 5, 2001; 276(41): 38108 - 38114. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
