权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Novel Transporter Responsible for Intestinal Glycerol Absorption : Characterization of Its Function and Physiological Role

负责肠道甘油吸收的新型转运蛋白：其功能和生理作用的表征

基本信息

批准号：
16590116
负责人：
YUASA Hiroaki
金额：
$ 2.24万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The uptake of glycerol in the everted sacs of the rat small intestine was highly saturable, suggesting the involvement of carrier-mediated transport. Although moderate passive transport component was also observed, it was found that carrier-mediated transport is prevailing at concentrations far lower than the Michaelis constant, where carrier-mediated transport is in the linear phase and most efficient. The glycerol carrier was further suggested to be of Na^+-dependent and secondary active, and specific to glycerol and some analogous compounds. It should also be noted that carrier-mediated glycerol transport is highly efficient, being comparable to D-glucose transport by SGLT1(sodium-dependent glucose transporter 1), which is well known for its very high efficiency. These characteristics of carrier-mediated glycerol transport were consistent with those in the closed loop and the perfused segment of the rat small intestine in situ. Thus, we successfully demonstrated the presence of a carrier-mediated transport system specific to glycerol and some analogous compounds in the rat intestinal tissue, and characterized it kinetically.HCT-15 is a human colon cancer cell line, which was found to be able to perform Na^+-dependent glycerol uptake in the present research project. Although the glycerol carrier in HCT-15 cells was suggested to be different from the one in the small intestine as there was a 50-fold difference in the Michaelis constants, the profiles of inhibition of glycerol transport by various compounds were quite similar, indicating similar characteristics in recognition of substrates and/or inhibitors. Therefore, it maybe possible to use HCT-15 cells for screening inhibitors and potential substrates. HCT-15 could still be a useful model cell line for studies to identify a group of Na^+-dependent glycerol carriers and to elucidate their transport mechanism. Such carriers would be of interest as possible pathways of drug delivery and targets of drug development.

大鼠小肠外翻囊对甘油的摄取是高度饱和的，表明参与了载体介导的转运。虽然也观察到中度被动转运组分，但发现载体介导的转运在远低于米氏常数的浓度下占主导地位，其中载体介导的转运处于线性阶段并且最有效。甘油载体具有Na^+依赖性和次级活性，并对甘油和某些类似物具有特异性。还应注意的是，载体介导的甘油转运是高效的，与通过SGLT 1（钠依赖性葡萄糖转运蛋白1）的D-葡萄糖转运相当，SGLT 1以其非常高的效率而闻名。载体介导的甘油转运的这些特征与大鼠小肠原位闭合袢和灌流段中的特征一致。因此，我们成功地证明了在大鼠肠组织中存在一种对甘油和一些类似化合物具有特异性的载体介导的转运系统，并对其进行了动力学表征。HCT-15是本研究项目中发现的一种能够进行Na^+依赖性甘油摄取的人结肠癌细胞系。虽然HCT-15细胞中的甘油载体与小肠中的甘油载体不同，因为米氏常数相差50倍，但各种化合物抑制甘油转运的特征非常相似，表明在识别底物和/或抑制剂方面具有相似的特征。因此，利用HCT-15细胞筛选抑制剂和潜在底物是可能的。HCT-15仍然可以作为一个有用的模型细胞系，用于鉴定一组Na^+依赖性甘油载体并阐明其转运机制的研究。这些载体将作为药物递送的可能途径和药物开发的靶点而受到关注。