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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Uptake properties of lamivudine (3TC) by a continuous renal epithelial cell line.
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Uptake properties of lamivudine (3TC) by a continuous renal epithelial cell line.

机译：连续肾上皮细胞系对拉米夫定（3TC）的吸收特性。

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摘要

The purpose of this study was to characterize the renal uptake properties of the cytidine analog and antiretroviral agent 3TC. The uptake of radiolabelled 3TC was measured at 37 degrees C in a continuous porcine renal epithelial cell line (i.e., LLC-PK1 cells) grown as a monolayer on an impermeable support. 3TC (5 microM) uptake (37 degrees C) by the monolayer cells was saturable (Km = 1.2 +/- 0.2 mM) but not significantly altered by various dideoxynucleoside analog drugs, nucleosides, and nucleoside transport inhibitors, suggesting that a nucleoside transporter is not involved in 3TC uptake. A number of endogenous organic cation probes and inhibitors significantly reduced 3TC uptake by the monolayer cells. Quinine, trimethoprim (TMP), and tetraethylammonium (TEA) inhibited 3TC uptake in a dose dependent manner with IC50 values of 0.6 mM, 0.63 mM, and 1.9 mM, respectively. In turn, the uptake of the typical organic cation substrate TEA was inhibited by high concentrations of 3TC. An outwardly directed proton gradient significantly increased the uptake of 3TC by the monolayer cells, suggesting the involvement of a proton exchange process. Conversely, in the presence of monensin, a Na+/H+ ionophore, the uptake of 3TC was significantly reduced. These results suggest that the uptake of 3TC by a cultured renal epithelium may be mediated by an organic cation-proton exchanger. The observed clinical interaction between 3TC and trimethoprim may be explained by competition for a common renal organic cation tubular transporter.
机译：这项研究的目的是表征胞苷类似物和抗逆转录病毒药物3TC的肾脏摄取特性。在不透性支持物上单层生长的连续猪肾上皮细胞系（即LLC-PK1细胞）中，于37摄氏度测量了放射性标记3TC的摄取。单层细胞对3TC（5 microM）的吸收（37摄氏度）是可饱和的（Km = 1.2 +/- 0.2 mM），但并没有被各种双脱氧核苷类似物药物，核苷和核苷转运抑制剂显着改变，表明核苷转运蛋白是不参与3TC吸收。许多内源性有机阳离子探针和抑制剂可显着降低单层细胞对3TC的吸收。奎宁，甲氧苄啶（TMP）和四乙铵（TEA）以剂量依赖性方式抑制3TC摄取，IC50值分别为0.6 mM，0.63 mM和1.9 mM。反过来，高浓度的3TC抑制了典型有机阳离子底物TEA的吸收。向外定向的质子梯度显着增加了单层细胞对3TC的吸收，表明涉及质子交换过程。相反，在莫能菌素（Na + / H +离子载体）存在下，3TC的吸收显着降低。这些结果表明，培养的肾上皮对3TC的摄取可能是由有机阳离子-质子交换剂介导的。观察到的3TC和甲氧苄氨嘧啶之间的临床相互作用可以通过竞争常见的肾脏有机阳离子肾小管转运蛋白来解释。

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