Expression of basolateral and canalicular transporters in rat liver and cultures of primary hepatocytes.
Basolateral and canalicular proteins are expressed in the liver and besides their role in the transport of bilirubin, glutathione, hormones and various glucuronides, they also function as transporters of a wide range of drugs. Despite their frequent use in drug research, little is known about the expression of genes coding for transporters in cultures of primary sandwiched hepatocytes. The kinetics of gene expression of canalicular and basolateral membrane transporters in cultures of primary rat sandwiched hepatocytes were investigated, and the expression of cMOAT, spgp, mdrla and mdr2 were shown to be comparable with transcript levels observed in vivo. Strikingly, expression of the basolateral membrane transporter ntcp and oatpl and 2 were dramatically reduced, the level being < 10 and < 5%, respectively, of those found in vivo in rat liver tissue. Notably, mRNA expression of the canalicular membrane transporter mdrlb was increased up to 13-fold. The findings point to a dramatic change in the expression of basolateral and canalicular transporters in cultured hepatocytes, and this should be considered when hepatocytes are used for drug profiling studies.
Borlak
J
J
Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology, Nikolai-Fuchs-Str. 1, D-30625 Hannover, Germany. borlak@item.fraunhofer.de
Klutcka
T
T
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000418:Albumins / Q000096:biosynthesis*; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D000418:Albumins; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C490548:Abcb11 protein, rat; C095122:multidrug resistance protein 3