Department of Clinical Pharmacokinetics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2–4–41 Ebara, Shinagawa-ku, Tokyo 142–8501, Japan.
Biol Pharm Bull. 2011;34(2):238-42. doi: 10.1248/bpb.34.238.
Aquaporin (AQP) 3 plays an important role in regulating faecal water content in the colon. We investigated the role of AQP3 in the colon in the laxative effect of magnesium sulphate (MgSO(4)), a widely used osmotic laxative. Rats were administered MgSO(4), after which faecal water content, the colon mRNA expression levels of sodium myo-inositol transporter (SMIT) and taurine transporter (TauT), the colon protein expression levels of AQP3 were examined. Faecal water content increased over time after MgSO(4) administration, and severe diarrhoea was observed between 4 and 8 h after administration. The mRNA expression levels of SMIT and TauT, which are indicators of variations in osmotic pressure, were highest at 2 h after the administration of MgSO(4) and were still elevated at 8 h after administration when compared to immediately after the administration. The immunostaining analysis showed that AQP3 is a dominant AQP in the rat colon. The protein expression levels of AQP3 in the colon increased over time following the administration of MgSO(4) and at 8 h after administration were approximately 8 times higher than baseline levels. Previously, osmotic laxatives were believed to induce diarrhoea by elevating the osmotic pressure in the intestinal tract. The results of the present study suggest that the laxative effect of MgSO(4) is not simply caused by a change in the osmotic pressure in the intestinal tract, but could be a response to increased expression of AQP3.
水通道蛋白 3(AQP3)在调节结肠粪便含水量方面发挥着重要作用。我们研究了 AQP3 在硫酸镁(MgSO4)——一种广泛应用的渗透性泻药——引起的结肠泻下作用中的作用。给大鼠施用硫酸镁后,检测粪便含水量、结肠钠肌醇转运体(SMIT)和牛磺酸转运体(TauT)mRNA 表达水平以及结肠 AQP3 蛋白表达水平。硫酸镁给药后粪便含水量随时间增加,给药后 4 至 8 小时出现严重腹泻。SMIT 和 TauT 的 mRNA 表达水平(反映渗透压变化的指标)在硫酸镁给药后 2 小时最高,与给药后即刻相比,8 小时时仍升高。免疫组化分析显示 AQP3 是大鼠结肠中的主要 AQP。硫酸镁给药后结肠 AQP3 蛋白表达水平随时间增加,给药 8 小时时的表达水平约为基线水平的 8 倍。之前,渗透性泻药被认为通过提高肠道内的渗透压来引起腹泻。本研究结果表明,硫酸镁的泻下作用并非仅仅是由于肠道渗透压的变化引起,可能是对 AQP3 表达增加的一种反应。