Carrier-mediated uptake of cisplatin by the OK renal epithelial cell line

The purpose of this study was to investigate whether transport of cis-diamm inedichloroplatinum II (cisplatin) across renal epithelial cell line OK cel ls is mediated by the organic cation transport system. OK cell monolayers c ultured on permeable membranes were incubated with 100 mu M cisplatin on th e apical or basolateral side, and the cellular accumulation and the transpo rt of cisplatin across the monolayer were measured. The accumulation from t he basolateral medium and the basolateral-to-apical transport of cisplatin were higher than the accumulation from the apical medium and the apical-to- basolateral transport, respectively. The cell monolayers were incubated wit h different concentrations of cisplatin (0.02 similar to 3 mM) in the basol ateral medium. The relationship between the cisplatin concentrations in the medium and in the cells revealed that cisplatin accumulation tended to be saturable. The basolateral-to-apical transport of cisplatin was increased w hen the pH of the apical medium was decreased, with a concomitant decrease in the accumulation of cisplatin. Coincubation of cisplatin with tetraethyl ammonium (TEA), a typical substrate for the organic cation transporter, sig nificantly decreased the accumulation and transport of cisplatin From the b asolateral medium. These results suggest that the uptake and basolateral-to -apical transport of cisplatin are mediated by not only simple diffusion bu t also by the organic cation transport system. (C) 2000 Elsevier Science Ir eland Ltd. All rights reserved.