Mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells
Mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells
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DOI：
10.1002/bdd.755
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发表时间：
2011-07-01
影响因子：
2.1
通讯作者：
Hashimoto, Yukiya
中科院分区：
文献类型：
--
作者：
Horie, Asuka;Sakata, Jumpei;Hashimoto, Yukiya
本研究的目的是研究二甲双胍在人肠上皮Caco-2细胞中的膜转运机制。Caco-2细胞不仅表达有机阳离子转运蛋白（OCT）3，而且还表达OCT 1和OCT 2。100 μ M二甲双胍在多孔滤膜上生长的Caco-2细胞的顶膜处的摄取显著大于在基底侧膜处的摄取。在塑料培养皿上生长的Caco-2细胞中，100 μ M二甲双胍的顶端摄取受到1 mM未标记二甲双胍、奎尼丁和吡拉明的显著抑制，表明Caco-2细胞中二甲双胍的顶端摄取涉及特定的转运系统。Caco-2细胞中100 μ M二甲双胍的顶端摄取通过培养基酸化而降低，但不通过碱化而增加。此外，在顶端培养基pH 8.4下，羰基氰4-（三氟甲氧基）苯腙（质子载体）对Caco-2细胞中二甲双胍的顶端摄取无影响。这些结果表明，二甲双胍在Caco-2细胞中的顶端摄取至少部分由OCT介导，但假定的H+/叔胺反向转运系统不负责二甲双胍的顶端摄取。版权所有（C）2011约翰威利父子有限公司
The aim of the present study was to investigate the mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells. The mRNA of not only organic cation transporter (OCT) 3, but also OCT1 and OCT2, was expressed in Caco-2 cells. The uptake of 100 mu M metformin at the apical membrane of Caco-2 cells grown on porous filter membrane was significantly greater than that at the basolateral membrane. The apical uptake of 100 mu M metformin in Caco-2 cells grown on plastic dishes was inhibited significantly by 1 mM unlabeled metformin, quinidine and pyrilamine, indicating that a specific transport system is involved in the apical uptake of metformin in Caco-2 cells. The apical uptake of 100 mu M metformin in Caco-2 cells was decreased by acidification of the medium, but not increased by alkalization. In addition, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (a protonophore) had no effect on the apical uptake of metformin in Caco-2 cells at apical medium pH 8.4. These findings suggested that the apical uptake of metformin in Caco-2 cells is mediated at least partly by OCTs, but that the postulated H+/tertiary amine antiport system is not responsible for the apical uptake of metformin. Copyright (C) 2011 John Wiley & Sons, Ltd.