Uptake of Doxorubicin by Cultured Kidney Epithelial Cells LLC-PK_1

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The renal handling of doxorubicin (DXR) was investigated using a kidney epithelial cell line, LLC-PK_1. The uptake of DXR by LLC-PK_1 cells cultured on plastic dishes was shown to be temperature and concentration dependent. The initial uptake of DXR was slightly saturable. The K_m and V_<max> of the saturable component were calculated to be 20.2 μM, and 0.355 nmol/mg protein/10 min, respectively. The release of DXR from LLC-PK_1 cells was very slow at 37℃ and almost negligible at 4℃, indicating that most of the DXR in the cells irreversibly binds to cellular constituents and that only a slight amount of unbound DXR participates in the efflux out of the cells. DXR uptake at 37℃ was significantly decreased in the presence of 2,4-dinitrophenol. However, organic cations and aminoglycoside antibiotics, such as tetraethylammonium, N^1-methylnicotinamide, guanidine, gentamicin and neomycin, did not inhibit DXR uptake, suggesting that a process distinct from the organic cation transport system and absorptive endocytosis might be involved in the uptake of DXR by LLC-PK_1 cells.
社団法人日本薬学会の論文
1998-05-15