Revisiting CFTR inhibition: a comparative study of CFTRinh -172 and GlyH-101 inhibitors.
Revisiting CFTR inhibition: a comparative study of CFTRinh -172 and GlyH-101 inhibitors.
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DOI：
10.1111/bph.12726
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发表时间：
2014-08
影响因子：
7.3
通讯作者：
Duranton C
中科院分区：
文献类型：
--
作者：
Melis N;Tauc M;Cougnon M;Bendahhou S;Giuliano S;Rubera I;Duranton C
几十年来，囊性纤维化跨膜传导调节因子（CFTR）氯离子通道的抑制剂已被用作研究CFTR传导在囊性纤维化研究中的作用和功能的工具。在21世纪初，两种新的有效的CFTR抑制剂CFTRinh-172和GlyH-101被描述，现在被广泛用于特异性抑制CFTR。然而，尽管有一些证据，这两种药物对其他类型的Cl−电导的影响被忽视了。在这种情况下，我们探讨的特异性和细胞毒性的抑制剂在CFTR表达和非CFTR表达细胞。使用膜片钳技术，我们测试了CFTRinh-172和GlyH-101抑制剂对三种不同类型的Cl−电流的影响：CFTR样电导，体积敏感外向整流Cl−电导（VSORC）和Ca 2+依赖性Cl−电导（CaCC）。我们还探索了两种抑制剂对细胞活力的影响，使用活/死和细胞增殖试验在两个不同的细胞系。我们证实这两种化合物是CFTR介导的Cl−电导的有效抑制剂。然而，GlyH-101在用于抑制CFTR的浓度下也抑制VSORC电导和CaCC。CFTRinh-172不影响CaCC，但在浓度高于5 μM时抑制VSORC。两种抑制剂（20 µM;暴露24 h）均不影响细胞活力，但在较高浓度下均具有细胞毒性。这两种抑制剂影响Cl−电导除了CFTR。我们的研究结果为它们在小鼠模型中的应用提供了见解。
For decades, inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel have been used as tools to investigate the role and function of CFTR conductance in cystic fibrosis research. In the early 2000s, two new and potent inhibitors of CFTR, CFTRinh-172 and GlyH-101, were described and are now widely used to inhibit specifically CFTR. However, despite some evidence, the effects of both drugs on other types of Cl−-conductance have been overlooked. In this context, we explore the specificity and the cellular toxicity of both inhibitors in CFTR-expressing and non–CFTR-expressing cells. Using patch-clamp technique, we tested the effects of CFTRinh-172 and GlyH-101 inhibitors on three distinct types of Cl− currents: the CFTR-like conductance, the volume-sensitive outwardly rectifying Cl− conductance (VSORC) and finally the Ca2+-dependent Cl− conductance (CaCC). We also explored the effect of both inhibitors on cell viability using live/dead and cell proliferation assays in two different cell lines. We confirmed that these two compounds were potent inhibitors of the CFTR-mediated Cl− conductance. However,GlyH-101 also inhibited the VSORC conductance and the CaCC at concentrations used to inhibit CFTR. The CFTRinh-172 did not affect the CaCC but did inhibit the VSORC, at concentrations higher than 5 µM. Neither inhibitor (20 µM; 24 h exposure) affected cell viability, but both were cytotoxic at higher concentrations. Both inhibitors affected Cl− conductances apart from CFTR. Our results provided insights into their use in mouse models.
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影响因子：
4.5
作者：
DISTEFANO, A;WITTNER, M;GREGER, R
通讯作者：
GREGER, R
影响因子：
2
作者：
Lu, Michael;Ding, Chuanqing
通讯作者：
Ding, Chuanqing
影响因子：
8.8
作者：
Peyronnet, Remi;Sharif-Naeini, Reza;Duprat, Fabrice
通讯作者：
Duprat, Fabrice
DOI：
10.1085/jgp.200409059
发表时间：
2004-08
期刊：
The Journal of general physiology
影响因子：
--
作者：
Muanprasat C;Sonawane ND;Salinas D;Taddei A;Galietta LJ;Verkman AS
通讯作者：
Verkman AS
影响因子：
11.2
作者：
Milosavljevic, Nina;Duranton, Christophe;Poet, Mallorie
通讯作者：
Poet, Mallorie