EXPRESSION OF THE CONJUGATE EXPORT PUMP ENCODED BY THE MRP2 GENE IN THE APICAL MEMBRANE OF KIDNEY PROXIMAL TUBULES

A novel ATP-dependent export pump for amphiphilic anionic conjugates, which has been cloned recently from liver, was identified in rat kidne y and localized to the apical membrane domain of proximal tubule epith elia. This 190-kD membrane glycoprotein (Mrp2) has been described prev iously as the hepatocyte canalicular isoform of the multidrug resistan ce protein and as the canalicular multispecific organic anion transpor ter. Mrp2 was identified in kidney by reverse transcription PCR follow ed by sequencing of the amplified 786-bp fragment and by immunoblottin g, using an antibody specifically reacting with the carboxy terminus o f rat Mrp2. Double immunofluorescence and confocal laser-scanning micr oscopy showed the presence of Mrp2 in the brush-border membrane domain of segments S-1, S-2, and S-3 of proximal tubule epithelia. Mrp2 was not detectable in other segments of the nephron. The onset of Mrp2 exp ression during development occurred in a very early stage of nephron d evelopment. Mrp2 represents the first cloned ATP-dependent export pump for amphiphilic organic anions identified in kidney and localized to the apical membrane domain of proximal tubule epithelia. Mrp2 may cont ribute to cellular detoxification and to the secretion of endogenous a nd xenobiotic anionic substances, most of which are conjugates, from t he blood into urine.