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Excerpt
Effects of pH of apical medium on accumulation and transport of cisplatin (CDDP) in cultured renal epithelial cells OK and LLC-PK1 were investigated. These cell monolayers, cultured on permeable membranes, were incubated for 60 min with 0.1 mM CDDP added to either the apical or basolateral incubation medium. pH of apical incubation medium was pH 5.5, 6.4 and 7.4 and that of basolateral medium was pH 7.4. In both cell monolayers, the decrease in pH of apical medium significantly increased both cellular accumulation of CDDP from the apical medium and the apical-to-basolateral transport of CDDP. The relationship between the cellular accumulation of CDDP and increased concentrations of CDDP in the apical medium (0.1 to 3 mM) was saturable (nonlinear), suggesting the involvement of carrier-mediated process. In contrast, the decrease in pH of apical medium significantly decreased the cellular accumulation of CDDP from the basolateral medium with an concomitant increase of the basolateral-to-apical transport of CDDP. These results suggest the pH-dependent influx and efflux of CDDP across the apical membrane of renal epithelial cells via specific mechanisms.
