The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages
The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages
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DOI：
10.1152/ajpgi.00286.2011
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Sugiyama, Kiyoshi
中科院分区：
文献类型：
--
作者：
Ikarashi, Nobutomo;Baba, Kohta;Sugiyama, Kiyoshi
[10]李文，李文.比沙可啶的通便作用归因于巨噬细胞分泌的PGE（2）增加诱导的结肠水通道蛋白-3表达降低。美国生理学杂志胃肠和肝脏生理学301：G887-G895，2011年。首次发表于2011年8月25日; doi：10.1152/ajpgi.00286.2011。本研究旨在探讨结肠水通道蛋白3（AQP 3）在比沙可啶通便作用中的作用。大鼠经口给予比沙可啶后，检查结肠中的AQP 3、巨噬细胞、环氧合酶2（COX 2）和前列腺素E-2（PGE（2））。使用HT-29和Raw 264.7细胞检查了比沙可啶降低AQP 3表达的机制。当腹泻发生时，观察到PGE（2）表达显著增加，而AQP 3表达降低。免疫组化显示COX 2仅在巨噬细胞中表达。在Raw 264.7细胞中加入比沙可啶后30 min，PGE（2）浓度显著升高。在HT-29细胞中加入PGE（2）30分钟后，AQP 3表达水平下降至对照的40%。当用吲哚美辛预处理时，比沙可啶不会引起结肠PGE（2）水平升高、AQP 3表达水平降低或腹泻。结果表明，比沙可啶可降低结肠中AQP 3的表达，从而抑制水从管腔侧转移到血管侧，并导致通便作用。这项研究还表明，比沙可啶直接激活结肠巨噬细胞可增加PGE（2）的分泌，PGE（2）作为一种旁分泌因子，可降低结肠粘膜上皮细胞中AQP 3的表达。
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 (PGE(2)) 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.