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  • Title: Effects of P-glycoprotein inhibitors on cadmium accumulation in cultured renal epithelial cells, LLC-PK1, and OK.
    Author: Endo T, Kimura O, Sakata M.
    Journal: Toxicol Appl Pharmacol; 2002 Dec 15; 185(3):166-71. PubMed ID: 12498733.
    Abstract:
    The purpose of this study was to investigate whether cadmium (Cd) efflux across the apical membrane of cultured renal epithelial cells, LLC-PK(1) and OK, is mediated via P-glycoprotein (P-gp). These cells were preincubated for 30 min with a typical P-gp inhibitor such as verapamil, diltiazem, nifedipine, vinblastine, or cyclosporin A before the incubation with 1 microM (109)CdCl(2) for 15 min. Preincubation with each P-gp inhibitor significantly increased Cd accumulation in LLC-PK(1), and OK cells. Treatment of these cells with UIC2, a P-gp monoclonal antibody, also significantly increased Cd accumulation in these cells. Thus, the pretreatment of cells with P-gp inhibitor appears to increase Cd accumulation as a result of the inhibition of Cd efflux via P-gp. To confirm Cd efflux via P-gp, Cd accumulation in P-gp-overexpressed cells (LLC-GA5-COL150 cells) was compared with that in parental LLC-PK(1) cells. LLC-GA5-COL150 cells accumulated less Cd than did LLC-PK(1) cells, and the effects of the P-gp inhibitors and UIC2 on Cd accumulation were greater in LLC-GA5-COL150 cells. These results suggest that P-gp in LLC-PK(1) and OK cells appear to act as an efflux pump of Cd, decreasing cellular Cd accumulation.
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