Acetazolamide reversibly inhibits water conduction by aquaporin-4
Acetazolamide reversibly inhibits water conduction by aquaporin-4
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DOI：
10.1016/j.jsb.2008.11.010
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发表时间：
2009-04-01
影响因子：
3
通讯作者：
Fujiyoshi, Yoshinori
中科院分区：
文献类型：
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作者：
Tanimura, Yukihiro;Hiroaki, Yoko;Fujiyoshi, Yoshinori
水通道蛋白-4 （AQP4）与水中毒、脑缺血或脑膜炎引起的细胞毒性脑水肿有关。因此，适合临床使用的AQP4抑制剂有望帮助预防脑水肿。在这里，我们报道了抑制剂对AQP4和AQP1重组为脂质体的水传导的影响。乙酰唑胺（Acetazolamide， AZA）是一种磺胺碳酸酐酶（CA）抑制剂，通过AQP4可逆地抑制水的渗透，但不通过AQP1。另一种与AZA化学结构相似的磺胺类CA抑制剂Methazolamide （MZA）对AQP4或AQP1的水传导无显著影响。因此，我们的研究结果表明，AZA是AQP4介导的水传导的可逆抑制剂，并表明AZA至少在一定程度上对AQP4具有特异性。因此，AZA可以作为开发用于临床应用的aqp4特异性抑制剂的先导化合物。(C) 2008爱思唯尔公司版权所有。
Aquaporin-4 (AQP4) has been implicated in cytotoxic brain edema resulting from water intoxication, brain ischemia or meningitis. AQP4 inhibitors suitable for clinical use would thus be expected to help protect against brain edema. Here, we report the effect of inhibitors on water conduction by AQP4 and AQP1 reconstituted into liposomes. Acetazolamide (AZA), an inhibitor of sulfonamide carbonic anhydrase (CA), reversibly inhibits water permeation through AQP4, but not through AQP1. Methazolamide (MZA), another sulfonamide CA inhibitor similar in chemical structure to AZA, shows no significant effect on water conduction by AQP4 or AQP1. Our results thus demonstrate that AZA acts as a reversible inhibitor for AQP4-mediated water conduction and indicate that AZA is specific, at least to some degree, for AQP4. AZA may thus serve as a lead compound for the development of AQP4-specific inhibitors for clinical applications. (C) 2008 Elsevier Inc. All rights reserved.