Sasaya M, Wada I, Shida M, Sato M, Hatakeyama Y, Saitoh H, Takada M
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Biol Pharm Bull. 1998 May;21(5):527-9. doi: 10.1248/bpb.21.527.
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.
利用肾上皮细胞系LLC-PK1研究了阿霉素（DXR）的肾脏处理情况。结果显示，在塑料培养皿上培养的LLC-PK1细胞对DXR的摄取具有温度和浓度依赖性。DXR的初始摄取略显饱和。饱和成分的米氏常数（Km）和最大反应速度（Vmax）分别计算为20.2微摩尔和0.355纳摩尔/毫克蛋白质/10分钟。在37℃时，LLC-PK1细胞中DXR的释放非常缓慢，在4℃时几乎可以忽略不计，这表明细胞内的大部分DXR不可逆地与细胞成分结合，只有少量未结合的DXR参与细胞外排。在2,4-二硝基苯酚存在的情况下，37℃时DXR的摄取显著降低。然而，有机阳离子和氨基糖苷类抗生素，如四乙铵、N1-甲基烟酰胺、胍、庆大霉素和新霉素，并不抑制DXR的摄取，这表明LLC-PK1细胞摄取DXR可能涉及一个不同于有机阳离子转运系统和吸收性内吞作用的过程。
