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    Keywords: review ; molecular ; PHASE-II ; HUMAN HEPATOCYTES ; ORGANIC ANION TRANSPORTER ; multidrug resistance ; MOLECULAR-MECHANISMS ; hepatobiliary transport ; TRANSPORTER ; EFFLUX PUMPS ; SUBFAMILY ; multidrug resistance protein ; phase II ; SALT EXPORT PUMP ; MUTANT RATS ; TRANSCELLULAR TRANSPORT ; VECTORIAL TRANSPORT ; uptake ; enzymology ; PHASE ; ENZYME ; methods ; MEMBERS ; CELL-LINES ; mechanisms ; hepatocytes ; resistance ; GLUTATHIONE ; TRANSPORT ; MRP2 ; SUBSTRATE-SPECIFICITY ; ATP-dependent transport ; MULTIDRUG-RESISTANCE ; cell lines ; CELL-LINE ; MEMBRANE ; LINE ; HUMAN LIVER ; MULTIDRUG-RESISTANCE PROTEIN ; LOCALIZATION ; DNA ; MECHANISM ; PROTEIN ; CLONING ; LINES ; TOOL ; SYSTEMS ; SYSTEM ; ENZYMES ; human ; VITRO ; IN-VITRO ; EXPRESSION ; BLOOD ; Germany
    Abstract: Conjugates of endogenous substances and of xenobiotics, formed extrahepatically or inside hepatocytes, undergo vectorial transport into bile. Substances conjugated with glucuronate, sulfate, or glutathione are substrates for organic anion uptake transporters in the basolateral (sinusoidal) membrane as well as substrates for the unidirectional ATP-driven conjugate efflux pump in the apical (canalicular) membrane, termed multidrug resistance protein 2 (MRP2; systematic name ABCC2). Localization of the efflux pumps ABCC3 and ABCC4 to the basolateral membrane of human hepatocytes has provided insight into the molecular mechanisms of conjugate efflux from hepatocytes into blood, as exemplified by the efflux of bilirubin glucuronosides mediated by ABCC3. The cloning and stable expression of the complementary DNAs encoding the organic anion transporters in the basolateral membrane of human hepatocytes and of members of the ABCC subfamily of efflux pumps in the apical as well as in the basolateral membrane have improved our understanding of hepatobiliary elimination and of the substrate specificity with respect to anionic conjugates. The stable expression of human hepatocyte uptake and efflux transporters in polarized cell lines, as described in this chapter, provides valuable tools for the in vitro analysis of human hepatobiliary transport in general and specifically for uptake and efflux of the anionic conjugates formed in various phase 2 reactions
    Type of Publication: Book chapter
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