Abstract
The renal handling of doxorubicin (DXR) was investigated using a kidney epithelial cell line, LLC-PK1. The uptake of DXR by LLC-PK1 cells cultured on plastic dishes was shown to be temperature and concentration dependent. The initial uptake of DXR was slightly saturable. The Km and Vmax of the saturable component were calculated to be 20.2 microM, and 0.355 nmol/mg protein/10 min, respectively. The release of DXR from LLC-PK1 cells was very slow at 37 degrees C and almost negligible at 4 degrees C, 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 degrees C was significantly decreased in the presence of 2,4-dinitrophenol. However, organic cations and aminoglycoside antibiotics, such as tetraethylammonium, N1-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-PK1 cells.
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