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  • Title: [The elucidation of the function and the expression control mechanism of aquaporin-3 in the colon].
    Author: Ikarashi N.
    Journal: Yakugaku Zasshi; 2013; 133(9):955-61. PubMed ID: 23995803.
    Abstract:
    Aquaporins (AQPs) are membrane channels that transport water within the human body and are therefore important for the regulation of water homeostasis. However, little is known regarding the details of the physiological role of AQP3, which is predominantly expressed in the colon. Thus, we investigated the role of AQP3 in the colon using laxative agents (magnesium sulfate and bisacodyl). The results suggest that the laxative effect produced by magnesium sulfate, which is classified as an osmotic laxative, is not simply a result of the changes in osmotic pressure but is also associated with the increased expression of AQP3 in the mucosal epithelial cells of the colon. In addition, magnesium sulfate increased colonic AQP3 expression through adenylate cyclase activation, which is caused by an increase in the intracellular Mg(2+) concentration. This effect may trigger CREB phosphorylation through PKA activation and promote AQP3 gene transcription. Meanwhile, bisacodyl, which is classified as a stimulant laxative, decreases the expression level of AQP3 in the mucosal epithelial cells of the colon, resulting in the inhibition of water transfer from the intestinal tract to the vascular side of the epithelium, eventually leading to the development of diarrhea. It was also observed that the direct activation of colon macrophages by bisacodyl increases the secretion of PGE2, which acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Future studies of the enteric AQP3 expression level and water transport may aid in the development of new laxative and antidiarrheal agents that target AQP3.
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