Bidirectional transport of cadmium across apical membrane of renal epithelial cell lines via H+-antiporter and inorganic anion exchanger

The purpose of this study was to investigate whether cadmium (Cd) efflux ac ross the apical membrane of renal epithelial cells is mediated via a H+-ant iport system, and to confirm the re-uptake of Cd from the apical membrane v ia an inorganic anion exchanger. LLC-PK1 and OK cell monolayers cultured on permeable membranes were incubated with 1 mu M CdCl2, added to the basolat eral medium, and the transport of Cd from the basolateral to apical medium and the accumulation of Cd in the monolayers were measured. Cd transport wa s increased by lowering the pH of the apical medium and was accompanied by a decrease in Cd accumulation. Coincubation with N'-methylnicotinamide or c isplatin, which act as substrates of the H+-antiport systems, decreased Cd transport and increased Cd accumulation in a concentration-dependent manner . To confirm the re-uptake of Cd, LLC-PK1, cell monolayers were pretreated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a specific in hibitor of an inorganic anion exchanger, before incubation with CdCl2,. Pre treatment with DIDS significantly increased Cd transport and decreased Cd a ccumulation at an apical medium pH of 7.4, but not at pH 5.5. These results suggest bidirectional transport of Cd across the apical membrane of renal epithelial cells via a H+-antiport system (efflux) and an inorganic anion e xchanger (influx), depending on the pH of the apical side. (C) 1998 Elsevie r Science Ireland Ltd. All rights reserved.