Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters

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• 作者：Takashi Yamamoto ; Kenichi Kuniki ; Yoh Takekuma ; Takeshi Hirano ; Ken Iseki ; Mitsuru Sugawara
• 关键词：Ribavirin ; Concentrative nucleoside transporter ; Equilibrative nucleoside transporter ; BeWo cells ; (Xenopus laevis) oocytes
• 刊名：European Journal of Pharmacology
• 出版年：2007
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：14 February 2007
• 卷：557
• 期：1
• 页码：1-8
• 文件大小：505 K

摘要

We investigated the mechanism of the transport of ribavirin (1-β-d-ribofuranosyl-1,2,4-trizole-3-carboxamide) into placental epithelial cells using human choriocarcinoma (BeWo) cells and Xenopus oocytes expressing human nucleoside transporters. In BeWo cells, when a relatively low concentration (123 nM) of ribavirin was used, both Na⁺-dependent uptake and -independent uptake of ribavirin were observed. On the other hand, when a higher concentration (100 μM) of ribavirin was used, Na⁺-independent uptake was observed, but there was only a slight Na⁺-dependent uptake. In Xenopus oocytes, influxes of ribavirin mediated by hCNT2 (concentrative nucleoside transporter 2), hCNT3 (concentrative nucleoside transporter 3), hENT1 (equilibrative nucleoside transporter 1) and hENT2 (equilibrative nucleoside transporter 2) were saturable, and apparent K_m values were 18.0 μM, 14.2 μM, 3.46 mM and 3.71 mM, respectively. These data indicate that hCNT2 and hCNT3 have higher affinity for ribavirin than do hENT1 and hENT2. Moreover, analysis by RT-PCR showed that BeWo cells express mRNA of hCNT3, hENT1 and hENT2. These results suggest that ribavirin is taken up by BeWo cells via both the high-affinity Na⁺-dependent transporter hCNT3 and the low-affinity Na⁺-independent transporters hENT1 and hENT2.