Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes.

摘要: We have previously shown that the multi-drug resistance protein (MRP) mediates ATP-dependent membrane transport of glutathione S-conjugates and additional amphiphilic organic anions. In present study we demonstrate expression MRP in hepatocytes where it functions hepatobiliary excretion. Analysis by reverse transcription-PCR human normal rat liver mRNA resulted two expected cDNA fragments MRP. Four different antibodies against reacted on immunoblots with glycoprotein about 190 kD from canalicular as well basolateral hepatocyte preparations. A polyclonal antibody directed carboxy-terminal sequence detected homolog liver. Double immunofluorescence microscopy confocal laser scanning showed presence Mrp lateral domains hepatocytes. The function mrp gene-encoded conjugate export pump was assayed plasma vesicles leukotriene C4 a high-affinity S-conjugate substrate. deficient membranes TR- mutant associated lack amplification one selective loss membranes. livers transport-deficient rats localized only to but not membrane. Our results indicate absence or an isoform is basis for hereditary defect excretion anionic conjugates hepatocyte.