The Elucidation of the Function and the Expression Control Mechanism of Aquaporin-3 in the Colon

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 eŠect produced by magnesium sulfate, which is classiˆed 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 eŠect may trigger CREB phosphorylation through PKA activation and promote AQP3 gene transcription. Meanwhile, bisacodyl, which is classiˆed 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 PGE 2 , 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.

Fluid resuscitation via the rectum ameliorates hemodynamic disorders through adjusting aquaporin expression in an experimental severe acute pancreatitis model

“…In addition, suppression of AQP-3 function may lead to diarrhea by increasing the fecal water content. Furthermore, the purgative action of magnesium sulfate changes the osmotic pressure and downregulates AQP-3 expression in mucosal epithelial cells of the colon, resulting from activation of adenylate cyclase by increasing the intracellular magnesium ion concentration (20,26). In the present study, normal rat colon tissues expressed low levels of AQP-3.…”

“…AQPs may participate in the adjustment of intestinal mucosal permeability and the rate of water absorption. Abnormalities of AQPs are known to be associated with Crohn's disease, ulcerative colitis, slow transit constipation and cholera (18)(19)(20)(21)(22)(23)(24). A previous study (12) and the results of the present study demonstrated that the expression of AQPs in colon tissues during SAP increased significantly, but in a diverse manner, and a negative correlation between AQP expression and the MAP was determined.…”

Protein Level and Infantile Diarrhea in a Postweaning Piglet Model

“…The inhibition of AQP1, AQP3, AQP8, and AQP10 in the ileum has shown the imbalance of water absorption and secretion. With a high casein diet, the expression of some aquaporins becomes inhibited, thereby increasing the fecal water content, and ultimately inducing diarrhea [46,47]. AQPs played an important role in the transition during diarrhea in many tissues.…”

Aquaporins in Health and Disease: An Overview Focusing on the Gut of Different Species

“…Furthermore, AQP3 localization has been observed in the large intestine at the level of the stratified and basolateral epithelia in the distal colon [26,28,29,51] and in the rectum, whereas no signal detection was found in the caecum [52]. AQP4 has also been found in humans, albeit with a very low immunoreactive signal [21].…”