Bioimaging and theory for drug absorption in living cells

一场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，已经产生了一种观察和测量活细胞中药物的新方法。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多色荧光染料分子的发展，它代表了早期显微镜家所依赖的选择性染色的现代版本。在本项目中，我们尝试用新型光学显微镜研究活细胞中药物吸收的生物成像。我们对这一课题有了各种新的发现。分别是：转染IgE受体对P815肥大细胞瘤细胞表面CD63抗原表达的研究；电中性离子载体（莫能菌素）对磷脂双层膜电导变化的研究；药物生理药代动力学模型的应用与展望；肝脏根据半乳糖表面密度识别的半乳糖化蛋白；介导β -内酰胺类抗生素在肠道和肾脏吸收的大鼠H^+/肽解转运体的克隆和表征。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收益。

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.