Ikarashi N, Baba K, Ushiki T, Kon R, Mimura A, Toda T, Ishii M, Ochiai W, Sugiyama K. The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE 2 secretion from macrophages. Am J Physiol Gastrointest Liver Physiol 301: G887-G895, 2011. First published August 25, 2011; doi:10.1152/ajpgi.00286.2011.-The purpose of this study was to investigate the role of aquaporin3 (AQP3) in the colon in the laxative effect of bisacodyl. After oral administration of bisacodyl to rats, AQP3, macrophages, cyclooxygenase 2 (COX2), and prostaglandin E 2 (PGE2) were examined in the colon. The mechanism by which bisacodyl decreases the expression of AQP3 was examined using HT-29 and Raw264.7 cells. When diarrhea occurred, a significant increase in the expression of PGE 2 and a decrease in AQP3 expression were observed. Immunostaining showed COX2 expression only in macrophages. The PGE 2 concentration increased significantly 30 min after the addition of bisacodyl to Raw264.7 cells. Thirty minutes after PGE 2 addition to HT-29 cells, the AQP3 expression level decreased to 40% of the control. When pretreated with indomethacin, bisacodyl did not induce an increase in the colon PGE 2 level, a decrease in the AQP3 expression level, or diarrhea. The results suggest that bisacodyl may decrease the expression of AQP3 in the colon, which inhibits water transfer from the luminal to the vascular side and leads to a laxative effect. This study also showed that 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. aquaporin-3; prostaglandin E 2; bisacodyl; cyclooxygenase IN RECENT YEARS, IT HAS BECOME increasingly clear that aquaporins (AQPs), water channels, are involved in water transport in the intestinal tract (20). There are currently 13 known types of AQPs in humans, AQP0 through AQP12, which are expressed in a variety of tissues (15). Several AQPs are expressed in the intestinal tract, and at least the following eight types are known to exist there: AQP1, AQP2, AQP3, AQP4, AQP7, AQP8, AQP9, and AQP10 (5, 7, 17, 23). The main AQPs expressed in the colon are AQP1, AQP2, AQP3, AQP4, and AQP8 (5,16,23). Of these, extensive research has been conducted on AQP3, which is considered to play an important role in the colon, especially regarding water transfer (13, 34). We have found that the administration of the osmotic laxative magnesium sulfate (MgSO 4 ) to rats increases the expression of AQP3 in the colon, and an increase in the expression of AQP3 plays an essential role in the laxative effect of MgSO 4 (11,12).Bisacodyl is classified as a stimulant laxative and is widely used to treat constipation. Bisacodyl increases the production of prostaglandin E 2 (PGE 2 ) in intestinal epithelial cells and inhibits the activity of Na ϩ -K ϩ -ATPase, and, as a result, the osmotic pressure in the intestinal tract increases. It is believed that this increase in osmoti...

Aquaporins (AQPs) play important roles in the water transport system in the human body. There are currently 13 types of AQP, AQP0 through AQP12, which are expressed in various organs. Many members of the AQP family are expressed in the intestinal tract. AQP3 is predominantly expressed in the colon, ultimately controlling the water transport. Recently, it was clarified that several laxatives exhibit a laxative effect by changing the AQP3 expression level in the colon. In addition, it was revealed that morphine causes severe constipation by increasing the AQP3 expression level in the colon. These findings have shown that AQP3 is one of the most important functional molecules in water transport in the colon. This review will focus on the physiological and pathological roles of AQP3 in the colon, and discuss clinical applications of colon AQP3.

Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia meansii) is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. The present study investigated the anti-obesity/anti-diabetic effects of AP using obese diabetic KKAy mice. KKAy mice received either normal diet, high-fat diet or high-fat diet with additional AP for 7 weeks. After the end of administration, body weight, plasma glucose and insulin were measured. Furthermore, mRNA and protein expression of obesity/diabetic suppression-related genes were measured in skeletal muscle, liver and white adipose tissue. As a result, compared to the high-fat diet group, increases in body weight, plasma glucose and insulin were significantly suppressed for AP groups. Furthermore, compared to the high-fat diet group, mRNA expression of energy expenditure-related genes (PPARα, PPARδ, CPT1, ACO and UCP3) was significantly higher for AP groups in skeletal muscle. Protein expressions of CPT1, ACO and UCP3 for AP groups were also significantly higher when compared to the high-fat diet group. Moreover, AP lowered the expression of fat acid synthesis-related genes (SREBP-1c, ACC and FAS) in the liver. AP also increased mRNA expression of adiponectin and decreased expression of TNF-α in white adipose tissue. In conclusion, the anti-obesity actions of AP are considered attributable to increased expression of energy expenditure-related genes in skeletal muscle, and decreased fatty acid synthesis and fat intake in the liver. These results suggest that AP is expected to be a useful plant extract for alleviating metabolic syndrome.

No abstract