Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl- channels
Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl- channels
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DOI：
10.1038/sj.bjp.0704159
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发表时间：
2001-08-01
影响因子：
7.3
通讯作者：
Okada, Y
中科院分区：
文献类型：
--
作者：
Fan, HT;Morishima, S;Okada, Y
1已知一些苯酚衍生物可阻断体积敏感性Cl（-）通道。然而，对双酚根皮素通道的影响，这是一种已知的葡萄糖单通道Ind阴离子反向通道的阻断剂，尚未研究。在本研究中。我们使用全细胞膜片钳技术研究了根皮素对体积敏感性Cl（-）通道的作用，并与cAMP激活的CFTR Cl（-）通道和Ca（2+）激活的Cl（-）通道进行了比较。2根皮素的细胞外应用（超过10 μ M）电压依赖性，并以浓度依赖性方式（IC（50）类似于30 μ M），抑制人上皮T84、肠407细胞和小鼠乳腺C127/CFTR细胞中由低渗激发激活的Cl（-）电流。3相反，在30 μ M时根皮素不能抑制T84和C127/CFTR细胞中环AMP激活的Cl（-）电流。较高浓度然而，根皮素（超过100 μ m）以电压依赖性方式部分抑制CFTR Cl（-）电流，4在30和300 μ m时，根皮素对T84细胞中离子霉素诱导的Ca（2+）依赖性Cl（-）电流没有抑制作用。5可以得出结论，根皮素在低浓度时优先阻断体积敏感性Cl-通道（低于100 μ m），并且在较高浓度下也抑制环AMP激活的Cl（-）通道，而根皮素不抑制上皮细胞中的Ca（2+）激活的Cl（-）通道。
1 Some phenol derivatives are known to block volume-sensitive Cl(-) channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport Ind anion antiport, have not been examined. In the present study. we investigated the effects of phloretin on volume-sensitive Cl(-) channels in comparison with cyclic AMP-activated CFTR Cl(-) channels Ind Ca(2+)-activated Cl(-) channels using the whole-cell patch-clamp technique.2 Extracellular application of phloretin (over 10 muM) voltage-independently, and in a concentration-dependent manner (IC(50) similar to 30 muM), inhibited the Cl(-) current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.3 In contrast, at 30 muM phloretin failed to inhibit cyclic AMP-activated Cl(-) currents in T84 and C127/CFTR cells. Higher concentrations (over 100 mum) of phloretin, however, partially inhibited the CFTR Cl(-) currents in a voltage-dependent manner,4 At 30 and 300 mum, phloretin showed no inhibitory effect on Ca(2+)-dependent Cl(-) currents induced by ionomycin in T84 cells.5 It is concluded that phloretin preferentially blocks volume-sensitive Cl- channels at low concentrations (below 100 mum) and also inhibits cyclic AMP-activated Cl(-) channels at higher concentrations, whereas phloretin does not inhibit Ca(2+)-activated Cl(-) channels in epithelial cells.