| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
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.
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