Inhibition of aquaporin-3 water channel in the colon induces diarrhea.
Inhibition of aquaporin-3 water channel in the colon induces diarrhea.
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DOI：
10.1248/bpb.35.957
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发表时间：
2012
影响因子：
2
通讯作者：
N. Ikarashi;R. Kon;Tomohiko Iizasa;N. Suzuki;R. Hiruma;Kiyomi Suenaga;T. Toda;M. Ishii;M. Hoshino;W. Ochiai;K. Sugiyama
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文献类型：
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作者：
N. Ikarashi;R. Kon;Tomohiko Iizasa;N. Suzuki;R. Hiruma;Kiyomi Suenaga;T. Toda;M. Ishii;M. Hoshino;W. Ochiai;K. Sugiyama
水通道蛋白（Aquaporin， AQP） 3主要在结肠中表达，被认为在调节结肠中粪便水分含量中起重要作用。本研究使用HgCl(2)和CuSO(4)检测了AQP3在结肠中的作用，已知HgCl(2)和CuSO(4)可抑制AQP3的功能。在大鼠直肠给药盐酸(2)或CuSO(4) 1小时后，测量粪便含水量。结果显示，HgCl(2)给药组粪便含水量显著增加，约为对照组的4倍，并出现严重腹泻。然而，在给药1 h后，未观察到渗透调节基因（肌醇钠转运体和牛磺酸转运体）mRNA表达水平以及AQP3蛋白表达水平和分布的变化(2)。在CuSO(4)给药组观察到类似的结果。本研究结果提示，结肠中AQP3功能的抑制可引起腹泻。因此，研究揭示了结肠中粪便含水量受水从管腔侧向血管侧转运的控制，这一过程是由AQP3介导的。我们的研究结果表明，一种调节AQP3在结肠中的功能或表达的药物可能是开发泻药的新靶点。
Aquaporin (AQP) 3, which is predominantly expressed in the colon, is considered to play an important role in regulating the fecal water content in the colon. In this study, the role of AQP3 in the colon was examined using HgCl(2) and CuSO(4), which are known to inhibit AQP3 function. The fecal water content was measured up to 1 h after the rectal administration of HgCl(2) or CuSO(4) to rats. The results showed that the fecal water content in the HgCl(2) administration group increased significantly to approximately 4 times that in the control group, and severe diarrhea was observed. However, no changes were observed in the mRNA expression level of the osmoregulatory genes (sodium myo-inositol transporter and taurine transporter) and the level and distribution of AQP3 protein expression, as determined 1 h after the administration of HgCl(2). Comparable results were observed in the CuSO(4) administration group. The results of this study indicated that the inhibition of AQP3 function in the colon caused diarrhea. Therefore, it has been revealed that the fecal water content in the colon is controlled by the transport of water from the luminal side to the vascular side, which is mediated by AQP3. Our findings suggest that a drug that modulates the function or expression of AQP3 in the colon may represent a new target for the development of laxatives.