Endogenous expression of liver-specific drug transporters for organic anions in the rat hepatocytoma fusion cell line HPCT-1E3.
HPCT-1E3 cells, a fusion cell line between primary rat hepatocytes and Fao Reuber hepatoma cells H35, are immortalized hybrid cells with many phenotypic properties of liver parenchyma including phase I and II metabolism and bile acid secretion. Selective elimination of endogenous compounds and drugs by the liver involves transport proteins that complementarily mediate uptake and efflux in co-operation with metabolism, but the study of this function is limited by the unavailability of an integrated in vitro model. Therefore, we investigated the expression of some important liver-specific import and export carrier proteins for organic anions in this cell line. RT-PCR analysis indicated gene expression of Oat2, Oatplal, Oatpla4, Oatplb2, Rfc-1/MTX-1, FOLR, Mrp1-6, mdr1, and Lrp. Uptake and efflux as well as inhibition studies confirmed the functional activity of Oat, Oatp, Rfc-1, Mrp, and Mdr carriers. In conclusion, the hepatocyte-like HPCT-1E3 cell line shows endogenous expression of all liver-specific carrier proteins for organic anions and may hence represent a valuable in vitro model for the study of transport phenomena and their regulation in hepatocytes.
Halwachs
Sandra
S
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 15, D-04103 Leipzig, Germany.
Kneuer
Carsten
C
Honscha
Walther
W
D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology*; D007700:Kinetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000378:metabolism
D027361:Organic Anion Transporters; D012235:Rhodamines