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 across the apical membrane of renal epithelial cells is mediated via a H+-antiport system, and to confirm the re-uptake of Cd from the apical membrane via an inorganic anion exchanger. LLC-PK1 and OK cell monolayers cultured on permeable membranes were incubated with 1 microM CdCl2 added to the basolateral medium, and the transport of Cd from the basolateral to apical medium and the accumulation of Cd in the monolayers were measured. Cd transport was increased by lowering the pH of the apical medium and was accompanied by a decrease in Cd accumulation. Coincubation with N'-methylnicotinamide or cisplatin, 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 inhibitor of an inorganic anion exchanger, before incubation with CdCl2. Pretreatment with DIDS significantly increased Cd transport and decreased Cd accumulation 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 exchanger (influx), depending on the pH of the apical side.