Takashi Ushiki

Hoshi University, Shinagawa, Tōkyō, Japan

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Publications (4)10.04 Total impact

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    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.
    AJP Gastrointestinal and Liver Physiology 08/2011; 301(5):G887-95. · 3.65 Impact Factor
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    ABSTRACT: We have suggested that an osmotic laxative, magnesium sulphate (MgSO(4)), may act as a cathartic in a very rational manner by increasing the aquaporin 3 (AQP3) expression level and by changing osmotic pressure in the colon. In this study, we examined the mechanism by which MgSO(4) increases the intestinal AQP3 expression level by using the human colon cancer HT-29 cell line. After the addition of MgSO(4) to HT-29 cells, the expression levels of AQP3 mRNA and protein were measured using real-time RT-PCR and western blotting, respectively. The intracellular Mg(2+) concentration, adenylate cyclase (AC) activity and protein kinase A (PKA) activity were also determined. The phosphorylated cAMP response element-binding protein (CREB) expression levels were determined by western blotting. The AQP3 mRNA expression level started to increase significantly at 1 h after MgSO(4) addition and peaked at 9 h, at a level 3 times as high as the control levels. The AQP3 protein expression level started to increase 6 h after the addition and reached a level almost twice as high as the control levels by hour 12. In the HT-29 cells treated with MgSO(4), there was a 1.4-fold increase in the intracellular Mg(2+) concentration, a 1.5-fold increase in AC activity, a 1.6-fold increase in PKA activity, and a significant increase in phosphorylation of the CREB. These results suggest that the AC activation caused by an increase in the intracellular Mg(2+) concentration may trigger CREB phosphorylation through PKA activation and promote AQP3 gene transcription.
    Life sciences 01/2011; 88(3-4):194-200. · 2.56 Impact Factor
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    ABSTRACT: 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.
    Biological & Pharmaceutical Bulletin 01/2011; 34(2):238-42. · 1.85 Impact Factor
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    ABSTRACT: The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM). As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice. These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.
    Xenobiotica 02/2010; 40(4):282-90. · 1.98 Impact Factor