Probenecid, a gout remedy, inhibits pannexin 1 channels
Probenecid, a gout remedy, inhibits pannexin 1 channels
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DOI：
10.1152/ajpcell.00227.2008
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发表时间：
2008-09-01
影响因子：
5.5
通讯作者：
Dahl, Gerhard
中科院分区：
文献类型：
--
作者：
Silverman, William;Locovei, Silviu;Dahl, Gerhard
丙磺舒是一种公认的治疗痛风的药物，被认为作用于有机阴离子转运蛋白，从而通过阻断尿酸盐再摄取影响肾脏中的尿酸排泄。丙磺舒也被证明影响ATP的释放，导致ATP释放涉及有机阴离子转运蛋白的建议。然而，其他药理学证据和染料摄取的观察表明ATP的非囊泡释放是由大的膜通道介导的，泛连接蛋白1是一个突出的候选者。在本研究中，我们表明，丙磺舒抑制电流介导的泛连接蛋白1通道在相同的浓度范围内观察到的抑制运输过程。丙磺舒不影响连接蛋白形成的通道。因此，丙磺舒允许区分由连接蛋白和泛连接蛋白形成的通道。
Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.