Department of Clinical Pharmacokinetics, Hoshi University, Shinagawa-ku, Tokyo, Japan.
Biol Pharm Bull. 2012;35(6):957-62. doi: 10.1248/bpb.35.957.
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.
水通道蛋白 3（AQP3）主要在结肠中表达，被认为在调节结肠内粪便含水量方面发挥着重要作用。在这项研究中，使用已知可抑制 AQP3 功能的 HgCl2 和 CuSO4 来研究 AQP3 在结肠中的作用。在向大鼠直肠给予 HgCl2 或 CuSO4 后 1 小时测量粪便含水量。结果表明，HgCl2 给药组的粪便含水量显著增加至对照组的约 4 倍，并且观察到严重腹泻。然而，在给予 HgCl2 1 小时后，没有观察到渗透压调节基因（肌醇钠转运体和牛磺酸转运体）的 mRNA 表达水平以及 AQP3 蛋白表达的水平和分布发生变化。在 CuSO4 给药组也观察到了类似的结果。这项研究的结果表明，结肠中 AQP3 功能的抑制会导致腹泻。因此，已经揭示出结肠内粪便含水量是由 AQP3 介导的从腔侧到血管侧的水转运来控制的。我们的研究结果表明，调节结肠中 AQP3 功能或表达的药物可能成为开发泻药的新靶点。
