The concomitant use of an osmotic laxative, magnesium sulphate, and a stimulant laxative, bisacodyl, does not enhance the laxative effect.

Patients with severe constipation are treated with combinations of several different laxatives. The purpose of this study is to examine whether the concomitant use of different laxatives enhances the laxative effect, using an osmotic laxative, magnesium sulphate (MgSO4), and a stimulant laxative, bisacodyl. The faecal water content of rats, to which MgSO4 and bisacodyl were coadministered, was lower than that in the MgSO4 group, while the change in the faecal water content over time was very similar to that in the bisacodyl group. The mRNA expression of the osmotic pressure marker, sodium/myo-inositol transporter, in the coadministration group 5h after the administration was significantly higher than that in the control group and almost equal to that in the MgSO4 group. The protein expression level of aquaporin-3 (AQP3), which plays an important role in water transfer, in the coadministration group decreased compared to the control group, as was the case in the bisacodyl group. The results of this study indicates that the coadministration of MgSO4 and bisacodyl does not enhance the laxative effect because the expression level of AQP3 in the colon in the coadministration group was almost equal to that in the bisacodyl group.

The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2 secretion from macrophages.

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.