PT  - JOURNAL ARTICLE
AU  - Jerzy Madon
AU  - Bruno Hagenbuch
AU  - Lukas Landmann
AU  - Peter J. Meier
AU  - Bruno Stieger
TI  - Transport Function and Hepatocellular Localization of mrp6 in Rat Liver
AID  - 10.1124/mol.57.3.634
DP  - 2000 Mar 01
TA  - Molecular Pharmacology
PG  - 634--641
VI  - 57
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/57/3/634.short
4100  - http://molpharm.aspetjournals.org/content/57/3/634.full
SO  - Mol Pharmacol2000 Mar 01; 57
AB  - The multidrug resistance-associated proteins (Mrps) constitute a family of cellular export pumps of the ATP-binding cassette transporter superfamily and play an important role in hepatobiliary excretion. We investigated the transport function and subcellular localization of mrp6, a novel member of the mrp family, in rat liver. Transport studies in vesicles isolated from mrp6 expressing Sf9 cells identified the anionic cyclopentapeptide and endothelin receptor antagonist BQ-123 as a substrate of mrp6 (K m ∼ 17 μM). Besides BQ-123, which is also a substrate of mrp2 (K m ∼ 124 μM), no other common substrates were found for mrp2, mrp6, and the canalicular bile salt export pump Bsep. The cyclic peptides endothelin I and Arg8-vasopressin were transported by mrp2 but not by mrp6. Using a polyclonal antiserum raised against a C-terminal peptide, mrp6 was found to be localized at the lateral and, to a lesser extent, at the canalicular plasma membrane of hepatocytes. The limited overlap of the substrate specificity with the canalicular export pumps mrp2 and Bsep indicates that mrp6 does not play a major role in canalicular organic anion excretion. However, its dual localization at the lateral and canalicular plasma membrane suggests that mrp6 might fulfill a “housekeeping” transport function involved in the regulation of paracellular and/or transcellular solute movement from blood into bile.