Functional expression of the rat liver canalicular isoform of the multidrug resistance‐associated protein

FEBS Letters

Madon, Jerzy¹  Eckhardt, Uta¹  Gerloff, Thomas¹  Meier, Peter J¹  Stieger, Bruno¹ 

[1] Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland

关键词: Multidrug resistance-associated protein;    Rat liver;    Canalicular transport;    Organic anion;    Glutathione conjugate;   

DOI  :  10.1016/S0014-5793(97)00245-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The rat hepatocanalicular isoform (called mrp2) of the human multidrug resistance-associated protein (MRP) has been cloned and transiently expressed in COS-7 cells and in Xenopus laevis oocytes. In both systems mrp2 expression induced a markedly increased efflux of intracellularly formed [¹⁴C]2,4-dinitrophenyl-S-glutathione. Injection of mrp2 cRNA into oocytes also stimulated efflux of [³H(N)]leukotriene C₄. Furthermore, mrp2 mRNA was markedly decreased in the liver of the transport mutant TR⁻ rat, which has a congenital defect in the biliary excretion of glutathione-S conjugates and of other divalent organic anions. The study provides a direct demonstration of mrp2-mediated transport function and supports the concept that mrp2 represents the canalicular multispecific organic anion transporter (cMOAT) of mammalian liver. © 1997 Federation of European Biochemical Societies.

【 授权许可】

Unknown