title: The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Kohta
authors.initials: K
authors.lastname: Baba
authors.forename: Takashi
authors.initials: T
authors.lastname: Ushiki
authors.forename: Risako
authors.initials: R
authors.lastname: Kon
authors.forename: Ayako
authors.initials: A
authors.lastname: Mimura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Toda
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishii
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D001726:Bisacodyl / Q000494:pharmacology*; D002400:Cathartics / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002400:Cathartics; D016861:Cyclooxygenase Inhibitors; D001726:Bisacodyl; D051400:Aquaporin 3; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007213:Indomethacin