Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid.
Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid.
复制标题
氯离子通道抑制剂茚满氧基乙酸可减弱内皮素的作用。
DOI：
10.1152/ajprenal.1992.262.5.f799
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Goligorsky,MS
中科院分区：
文献类型：
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作者：
Takenaka,T;Epstein,M;Forster,H;Landry,DW;Iijima,K;Goligorsky,MS
我们最近提出内皮素（ET）的作用部分是通过开放氯通道介导的（K。饭岛湖Lin，L. Nasjletti和M. S.哥利哥斯基Am. J.Physiol.260（Cell Physiol.29：C982-C992，1991）。在本研究中，氯离子通道抑制剂，茚满基氧基乙酸（IAA-94），阻止ET诱导的影响的能力，在培养的血管平滑肌细胞（VSMC）的荧光分光光度法和直接视频显微镜可视化的肾微循环在离体灌注积水肾（IPHK）。异硫氰酸荧光素（FITC）标记的IAA-94类似物显示特异性结合VSMC。IAA-94（30 μ M）既不影响VSMC的基础胞浆钙浓度（[Ca 2 +]i），也不影响对ET的峰值反应，但它显着减少了[Ca 2 +]i的持续升高（对照组的半衰期恢复为147 +/- 23 vs 248 +/- 33 s，P <0.05）。IAA-94使ET诱导的膜去极化从24.5 +/- 3.3 mV减弱至8.0 +/- 1.8 mV。在IPHK中，ET使传入小动脉（AA）收缩29 +/- 2%（18.7 +/- 0.8至13.2 +/- 0.6微米，P <0.001）。伊拉地平逆转了ET诱导的血管收缩。用IAA-94预处理不改变AA直径，但显著减弱ET诱导的AA收缩（AA直径仅减少9 +/-2%，P <0.001）。随后加入伊拉地平（0.1-1 μ M）不会进一步扩张AA。我们的数据表明，IAA-94显着衰减AA血管收缩引起的ET和建议，ET诱导的氯离子通道开放，膜去极化，和随后的激活电压依赖性钙通道有助于这种肽的血管收缩机制。
We have recently proposed that the actions of endothelin (ET) are in part mediated by opening of chloride channels (K. Iijima, L. Lin, A. Nasjletti, and M. S. Goligorsky. Am. J. Physiol. 260 (Cell Physiol. 29: C982-C992, 1991). In the present study the ability of a chloride channel inhibitor, an indanyloxyacetic acid (IAA-94), to block ET-induced effects was examined in cultured vascular smooth muscle cells (VSMC) by spectrofluorometry and direct videomicroscopic visualization of the renal microcirculation in isolated perfused hydronephrotic kidneys (IPHK). A fluorescein isothiocyanate (FITC)-labeled IAA-94 analogue showed specific binding to VSMC. IAA-94 (30 microM) neither affected basal cytosolic calcium concentration ([Ca2+]i) in VSMC nor peak response to ET, but it significantly curtailed sustained elevation of [Ca2+]i (half-time recovery was 147 +/- 23 vs. 248 +/- 33 s in control, P less than 0.05). IAA-94 blunted ET-induced membrane depolarization from 24.5 +/- 3.3 to 8.0 +/- 1.8 mV. In IPHK, ET constricted afferent arterioles (AA) by 29 +/- 2% (18.7 +/- 0.8 to 13.2 +/- 0.6 microns, P less than 0.001). Isradipine reversed this ET-induced vasoconstriction. Pretreatment with IAA-94 did not alter AA diameter, but markedly attenuated ET-induced AA constriction (reduction of AA diameters by only 9 +/- 2%, P less than 0.001). The subsequent addition of isradipine (0.1-1 microM) did not further dilate AA. Our data indicate that IAA-94 markedly attenuates AA vasoconstriction elicited by ET and suggest that ET-induced opening of chloride channels, membrane depolarization, and subsequent activation of voltage-dependent calcium channels contribute to the vasoconstrictor mechanisms of this peptide.