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

吸附介导的转运系统(AMTS)一直被认为是最有利的系统之一，将脑脊液中的肽和蛋白质输送到大脑中。本研究的目的是在功能和分子水平上阐明多肽和蛋白质在血脑屏障(BBB)中的吸附介导转运系统(AMTS)。在2002年的研究中，用永生化的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，碱性成纤维细胞生长因子是一种相对较大的分子(18 KDa)。结果发现，碱性成纤维细胞生长因子通过肝素敏感的内吞系统内化到TM-bbb4中。此外，还发现了一种热休克蛋白多糖，它表达于TM-BBB4细胞表面和脑毛细血管。因此，HSPG介导的碱性成纤维细胞生长因子转运系统在血脑屏障起着AMTS的作用。在2003年的研究中，研究了一种小的四肽[D-Arg^2]德吗啡类似物Tapa的转运功能。在体内，TPA通过血脑屏障被大脑摄取。此外，TAPA以浓度-2、温度和能量依赖的方式内化到TM-BBB4细胞中。这种内化可被阳离子多肽抑制，但不能被阴离子多肽和肝素抑制。这些结果表明，TAPA是由AMTS通过血脑屏障转运的，而不是bFGFs系统。在上述研究中，有人建议BBB至少有两种类型的AMT。

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.