2003 Fiscal Year Final Research Report Summary
Functional and Molecular Analysis of Peptide/Protein Transport System in the Blood-Brain Barrier
| Project/Area Number |
14572161
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Teikyo University |
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Principal Investigator |
DEGUCHI Yoshiharu Teikyo University, Pharmaceutical Science, Associate Professor, 薬学部, 助教授 (40254255)
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| Project Period (FY) |
2002 – 2003
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| Keywords | blood-brain barrier / adsorptive-mediated transport / heparan sulfate proteoglycan / immortalized cells / peptide transport system / opioid peptides / basic fibroblast growth factor / endocytosis |
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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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