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

Biological & Pharmaceutical Bulletin

Ogiue

Toyoda

et al. 2013

Self Cite

Aquaporin-3 (AQP3) plays an important role in maintaining the normal water content of the skin. Previously, we revealed that the expression of cutaneous AQP3 increased following oral administration of Gypsum fibrosum (main component: CaSO 4 ) to mice. The purpose of this study is to elucidate the mechanism by which Gypsum fibrosum increases the expression of cutaneous AQP3 in a keratinocyte cell line. Gypsum fibrosum or CaSO 4 was added to keratinocytes, and the expression level of AQP3, the Ca concentration, the activity of protein kinase C (PKC), and the degrees of phosphorylation of both extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were measured. The mRNA and protein expression levels of AQP3 increased significantly 6 h-post addition of Gypsum fibrosum. In keratinocytes treated with Gypsum fibrosum, increases in the concentration of intracellular Ca, PKC activity, and the phosphorylation of ERK and CREB were observed. Pre-treatment with GF109203X, a PKC inhibitor, suppressed the mRNA expression levels of AQP3. Similarly to treatment with Gypsum fibrosum, the addition of CaSO 4 led to the same observations in keratinocytes. It is hypothesized that Gypsum fibrosum causes an increase in the intracellular Ca concentration, PKC activity, and the phosphorylation levels of ERK and CREB, resulting in increased AQP3 expression in keratinocytes. In addition, it is possible that the effect of Gypsum fibrosum is attributable to CaSO 4 , based on the results demonstrating that the mechanisms of action of Gypsum fibrosum and CaSO 4 were nearly identical.

Section: Effects Of Gypsum Fibrosum or Caso 4 On The Expressionmentioning

confidence: 99%

Elucidating the Mechanism by Which <i>Gypsum fibrosum</i>, a Traditional Chinese Medicine, Maintains Cutaneous Water Content

Biological & Pharmaceutical Bulletin

Ogiue

Toyoda

et al. 2013

Self Cite

“…10,11) In addition, we have revealed that bisacodyl, which is classified as a stimulant laxative, decreases the expression of AQP3 in the mucosal epithelial cells of the colon, which results in the inhibition of water transfer from the intestinal tract to the vascular side and eventually leads to the development of diarrhea. 12,13) Based on these results, it has become clear that the changes in AQP3 expression cause changes in the water transport ability of the colon. However, there have been no reports that examined the effect of changes in the function of AQP3 on the transport of water in the colon in detail.…”

mentioning

confidence: 97%

Inhibition of Aquaporin-3 Water Channel in the Colon Induces Diarrhea

Biological & Pharmaceutical Bulletin

Kon

Iizasa

et al. 2012

Self Cite

Aquaporin (AQP) 3, which is predominantly expressed in the colon, is considered to play an important role in regulating the fecal water content in the colon. In this study, the role of AQP3 in the colon was examined using HgCl(2) and CuSO(4), which are known to inhibit AQP3 function. The fecal water content was measured up to 1 h after the rectal administration of HgCl(2) or CuSO(4) to rats. The results showed that the fecal water content in the HgCl(2) administration group increased significantly to approximately 4 times that in the control group, and severe diarrhea was observed. However, no changes were observed in the mRNA expression level of the osmoregulatory genes (sodium myo-inositol transporter and taurine transporter) and the level and distribution of AQP3 protein expression, as determined 1 h after the administration of HgCl(2). Comparable results were observed in the CuSO(4) administration group. The results of this study indicated that the inhibition of AQP3 function in the colon caused diarrhea. Therefore, it has been revealed that the fecal water content in the colon is controlled by the transport of water from the luminal side to the vascular side, which is mediated by AQP3. Our findings suggest that a drug that modulates the function or expression of AQP3 in the colon may represent a new target for the development of laxatives.

“…for 6 rats. Dunnett's test:  p＜0.05,   p＜0.01, and    p＜0.001 vs. 0 h. Modiˆed from Ikarashi et al17) …”

mentioning

confidence: 98%

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

2013

YAKUGAKU ZASSHI

Self Cite

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.