Inhibition of aquaporin-3 water channel in the colon induces diarrhea

Abstract

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 HgCl2 and CuSO4, which are known to inhibit AQP3 function. The fecal water content was measured up to 1 h after the rectal administration of HgCl2 or CuSO4 to rats. The results showed that the fecal water content in the HgCl2 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 HgCl2. Comparable results were observed in the CuSO4 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. © 2012 The Pharmaceutical Society of Japan.