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Bioimaging and theory for drug absorption in living cells

活细胞药物吸收的生物成像和理论

基本信息

批准号：
06304044
负责人：
NAKANISHI Mamoru
金额：
$ 2.37万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06304044/
关键词：
Durg absorption Confocal Microscopy Scanning Probe Microscopy Investigation of New Drug Absorption and Transportion Optical microscopic technique 顕微光学技術経皮吸収初回通回効果高分子薬物

项目摘要

A renaissance and a revolution in light microscopy are now under way. Several new technologies, used in conjunction with the light microscope, have yeilded a new way of seeing and measuring drugs in living cells. One major contribution to the new methodology is the use of computers for the digital processing and analysis of images. The second vital innovation in the new microscopy is the development of multicolor fluorescent dye molecules which represent a modern version ofselective stains relies on by earlier generations of microscopists. In this projects we have tried to study bioimaging for drug a bsorption in living cells by new light microscopes. We obtained various new findings for this subject. They were the studies of the surface expression of CD63 antigen in P815 mastocytoma cells by transfected IgE receptors, the conducance change in phospholipid bilayr membrace by an electroneutral ionophore (monensin), the application and prospects for physiologically based pharmacokinetic models involving pharmaceutical agents, the galactosylated proteins recognized by the liver according to the surface density of galactose, and cloning and characterization of rat H^+/peptidecotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. Thus, the present Grant-in-Aid for Co-operative Research was able to obtain an extreemly high gool in the field of drug absorption in living cells.

光学显微镜的复兴和革命正在进行中。几项新技术与光学显微镜结合使用，为观察和测量活细胞中的药物提供了一种新的方法。对新方法的一个主要贡献是使用计算机对图像进行数字处理和分析。新显微镜的第二个重要创新是荧光染料分子的发展，它代表了早期显微镜学家所依赖的选择性染色的现代版本。在本项目中，我们尝试用新的光学显微镜研究活细胞中药物吸附的生物成像。我们在这个课题上获得了许多新的发现。分别对转染IgE受体的P815肥大细胞瘤细胞表面CD 63抗原表达、电中性离子载体介导的磷脂双层膜电导变化进行了研究（莫能菌素），涉及药物制剂的基于生理学的药代动力学模型的应用和前景，根据半乳糖的表面密度由肝脏识别的半乳糖基化蛋白，大鼠H^+/肽转运蛋白介导β-内酰胺类抗生素在肠道和肾脏中吸收的克隆和鉴定。因此，目前的合作研究补助金能够在活细胞药物吸收领域获得极高的回报。