阳离子离子液体对人MATE1的底物依赖性抑制作用。
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马丁内斯-格雷罗LJ，赖特SH
阳离子离子液体对人MATE1的底物依赖性抑制作用。
中国药理学杂志，2013,31(3):495-503。doi: 10.1124 / jpet.113.204206。Epub 2013年6月19日。
- PubMed ID
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23785176 (PubMed视图]
- 摘要
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多药和毒素挤出剂1-和2-K (MATE1和MATE2-K)在肾近端小管细胞的管腔膜中表达，并在分泌生理pH值下携带净正电荷的分子(所谓的有机阳离子)中提供活跃步骤。本研究测试了当与结构不同的配体相互作用时，结构不同的MATE底物是否能表现出不同的抑制定量特征。所测试的配体是三种结构相似的阳离子离子液体(ILs)，液态盐:n -丁基吡啶，NBuPy;1-methyl-3-butylimidazolium Bmim;和n -丁基- n -甲基吡咯烷鎓，BmPy)。使用稳定表达MATE1或MATE2-K的中国仓鼠卵巢细胞来测量摄取。通过反式刺激，所有三种il都被两种MATE转运体转运。这三种il还抑制了三种结构不同的MATE底物:1-甲基-4-苯基吡啶(MPP)、三乙基甲基铵(TEMA)和N,N,N-三甲基-2-[甲基(7-硝基苯并[c][1,2,5]恶二唑-4-基)氨基]乙胺(NBD-MTMA)的吸收。MATE1对吡啶基NBuPy的亲和力(IC50值为2 ~ 4微米)高于对吡啶基NBuPy (BmPy;20-70微米)或咪唑基il (Bmim; 15-60 microM). Inhibition of MPP, TEMA, and NBD-MTMA transport by NBuPy was competitive, with comparable Ki values against all substrates. Bmim also competitively blocked the three substrates but with Ki values that differed significantly (20 microM against MPP and 30 microM against NBD-MTMA versus 60 microM against TEMA). Together, these data indicate that renal secretion of ILs by the human kidney involves MATE transporters and suggest that the mechanism of transport inhibition is ligand-dependent, supporting the hypothesis that the binding of substrates to MATE transporters involves interaction with a binding surface with multiple binding sites.