| Project/Area Number |
10470507
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | TOHOKU UNIVERSITY |
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Principal Investigator |
TERASAKI Tetsuya New Industry Creation Hatchery Center, Tohoku University, Professor, 未来科学技術共同研究センター, 教授 (60155463)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOYA Ken-ichi Graduate School of Pharmaceutical Sciences, Tohoku University, Assistant Professor, 大学院・薬学研究科, 助手 (70301033)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | blood-brain-barrier / blood-cerebrospinal fluid barrier / cerebral detoxification / efflux transport / acidic amino acid / estorone sulfate / System Xc / organic anion transport system / L-アスパラギン酸 / D-アスパラギン酸 / oatp2 / P-糖蛋白 / 分子多様性 / ステロイド / シスチン / グルタミン酸 |
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| Research Abstract |
The purpose of the present study is to provide evidences for the principle investigator's hypothesis that blood-brain barrier (BBB) has several efflux transport systems which play an important role for the detoxification of central nervous system (CNS). Employing brain efflux index (BEI) method, the BBB efflux rate of several substrates was determined. 1. Taurocholic acid was transported form the brain to the circulating blood via a carrier-mediated system which is different from that of para-aminohippuric acid. This transport system may play an important role to protect the CNS from the penetration of bile acids in the plasma to the brain. 2. L-Aspartic acid was significantly transported from the brain to the circulating blood, but D-aspartic acid was not. These results suggest that the BBB play an important role to pump out acidic amino acid, a neurotransmitter, from the brain to the circulating blood as a rescue system for the cerebral toxicity of these neurotransmitters. 3. Estrone sulfate and dehydroepiandrosterone sulfate were selectively transported from the brain to the blood. Organic anion transport protein (oatp 2) would be responsible for the efflux transport of these organic anions in the brain. 4. BQ123, a cyclic peptidomimetic drug was transported from the brain to the blood via a carrier-mediated system which is different from efflux systems for taurocholic acid, para-aminohippuric acid. Although it is necessary to clarify the detailed mechanisms for transport systems, it would be responsible for the non-specific penetration of the xenobiotics into the brain from the blood. Based on these several findings, it would be possible to conclude that the BBB play an important role as a detoxifying system by pumping out of bile acids, acidic amino acids, sulfo-conjugates of steroid hormone and hydrophobic xenobiotics.
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