Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia

Background & Aims: The multidrug resistance protein (MRP) isoforms MRP2 (AB CC2) and MRP3 (ABCC3) play a decisive role in the hepatic secretion of endo genous and xenobiotic conjugates and are differentially expressed in hepato cytes and cholangiocytes. The epithelium of the gallbladder considerably mo difies the composition of primary hepatic bile by absorption and secretion; however, the underlying transport mechanisms were largely unknown. Localiz ation of MRP2 and MRP3 may provide an explanation of how the products of ph ase II conjugation are effluxed from gallbladder epithelia. Methods: Expres sion and localization of MRP2 and MRP3 were analyzed by reverse-transcripti on polymerase chain reaction (RT-PCR) and immunofluorescence microscopy of human gallbladder tissue. Results: Expression of MRP2 and MRP3 was identifi ed in all gallbladders by RT-PCR followed by sequencing of the amplified fr agments. Double immunofluorescence microscopy using 2 specific antibodies f or the respective MRP isoform showed the simultaneous expression of MRP2 in the apical membrane and MRP3 in the basolateral membrane of gallbladder ep ithelia. MRP1 protein expression was not detectable. Conclusions: Our findi ngs show the expression of MRP2 and MRP3 in distinct plasma membrane domain s of gallbladder epithelia and provide evidence for the capacity of the gal lbladder to secrete xenobiotic and endogenous anionic conjugates into blood via MRP3 and into bile via MRP2.