Functional and Molecular Analysis of Peptide/Protein Transport System in the Blood-Brain Barrier

吸附介导转运系统（AMTS）一直被认为是最有利的系统之一，以运送pep - tides和蛋白质到大脑。本研究的目的是在功能和分子水平上阐明血脑屏障（BBB）中多肽和蛋白质的吸附介导转运系统（AMTS）。在2002年的研究中，利用永生化小鼠脑毛细血管内皮细胞（TM-BBB4）检测了碱性成纤维细胞生长因子（bFGF）的转运功能，bFGF是一种相对大分子（18 kDa）的碱性多肽。结果发现bFGF通过肝素敏感的内吞系统内化到TM-BBB4中。此外，我们还发现一种HSPG perlecan在TM-BBB4细胞和脑毛细血管表面表达。因此，hspg介导的bFGF转运系统在血脑屏障中起AMTS的作用。在2003年的研究中，研究了[D-Arg^2] dermorphin类似物TAPA（一种小的四肽）的转运功能。在体内，TAPA通过血脑屏障被大脑吸收。此外，TAPA以浓度-2温度-能量依赖的方式内化到TM-BBB4细胞中。这种内化被阳离子肽抑制，而不被阴离子肽和肝素抑制。这些结果表明，除了bFGF系统外，TAPA通过AMTS通过血脑屏障转运。上述研究提示血脑屏障处至少存在两种类型的AMTS。

The adsorptive-mediated transport system (AMTS) has been believed to be one of the most advantageous system for the delivery of the pep tides and protein to the brain. The objective in this research is to clarify the adsorptive-mediated transport system (AMTS) of peptides and proteins in the blood-brain barrier (BBB) at the functional and molecular levels. in 2002 study, the transport function of basic fibroblast growth factor (bFGF), a basic peptides which is relatively large molecule (18 kDa), was examined using an immortalized mouse brain capillary endothelial cells (TM-BBB4). As a result, it was found that bFGF is internalized into TM-BBB4 via a heparin-sensitive endocytosis system. In addition, it was found that perlecan, a HSPG, is expressed on the surface of TM-BBB4 cells and the brain capillary. Accordingly, it was suggested that HSPG-mediated transport system for bFGF was functioning at the BBB as an AMTS. In 2003 study, the transport function of [D-Arg^2] dermorphin analog TAPA, a small tetra peptide, was examined. TAPA was taken up by the brain via the BBB in vivo. in addition, TAPA was internalized into TM-BBB4 cells in concentration-2 temperature-, energy-dependent manner. This internalization was inhibited by cationic peptides, but not anionic peptide and heparin. These results suggest that TAPA was transported through the BBB by the AMTS, apart form the system for bFGF. In the above study, it was suggested that there area at least, two types of AMTS at the BBB.