Functional expression of the rat liver canalicular isoform of the multidrug resistance-associated protein.
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.
Madon
J
J
Department of Medicine, University Hospital, Zurich, Switzerland.
Eckhardt
U
U
Gerloff
T
T
Stieger
B
B
Meier
P J
PJ
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D003001:Cloning, Molecular; D004137:Dinitrochlorobenzene / Q000378:metabolism; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D004137:Dinitrochlorobenzene; D017997:Leukotriene C4; D027425:ATP-Binding Cassette, Sub-Family C Proteins