Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
复制标题
DOI：
--
复制
发表时间：
1990-05
影响因子：
3.6
通讯作者：
M. M. White-M.;M. Aylwin
中科院分区：
文献类型：
--
作者：
M. M. White-M.;M. Aylwin
研究了尼氟灭酸和氟芬那酸对爪蟾卵母细胞Ca ~（2+）激活的Cl ~-电流（ICl（Ca））的影响。这两种化合物可逆地抑制ICl（Ca），引起响应于去极化电压阶跃，以剂量依赖性的方式，与电流-电压曲线的形状没有影响。尼氟灭酸的表观抑制常数为17 μ M，而氟灭酸的表观抑制常数为28 μ M。尼氟灭酸还抑制了通过将Ca 2+浴加到使用Ca 2+离子载体A23187透化的卵母细胞中引起的ICl（Ca），表明ICl（Ca）的抑制是由于与Cl-通道的直接相互作用，而不是通过干扰通过电压依赖性Ca 2+通道的Ca 2+进入。当非洲爪蟾卵母细胞用作外源性离子通道和受体的表达系统时，除了它们在消除作为伪影的可能来源的ICl（Ca）中的用途之外，预期这两种化合物将用作有效的阴离子通道阻断剂。
The effects of niflumic acid and flufenamic acid, two nonsteroidal anti-inflammatory agents known to block anion transport in red blood cells, on Ca2(+)-activated Cl- currents (ICl(Ca)) in Xenopus oocytes were examined. Both compounds reversibly inhibited ICl(Ca), elicited in response to depolarizing voltage steps, in a dose-dependent manner, with no effect on the shape of the current-voltage curve. The apparent inhibition constant for niflumic acid was 17 microM, whereas that for flufenamic acid was 28 microM. Niflumic acid also inhibited ICl(Ca) elicited by bath application of Ca2+ to oocytes permeabilized using the Ca2+ ionophore A23187, demonstrating that the inhibition of ICl(Ca) is due to a direct interaction with the Cl- channel, rather than by interference with Ca2+ entry through voltage-dependent Ca2+ channels. In addition to their use in the elimination of ICl(Ca) as a possible source of artifact when Xenopus oocytes are used as an expression system for exogenous ion channels and receptors, it is expected that these two compounds will find use as potent anion channel blockers.