| Project/Area Number |
14207104
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 Tohoku University, New Industry Creation Hatchery Center, 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) |
OHTSUKI Sumio Tohoku University, Graduate School of Pharmaceutical Sciences, Assistant, 大学院・薬学研究科, 助教授 (60323036)
ASASHIMA Tomoko Tohoku University, Graduate School of Pharmaceutical Sciences, Research Instructor, 大学院・薬学研究科, 助手 (00400268)
KAMIIE Junichi Tohoku University, Graduate School of Pharmaceutical Sciences, Research Instructor, 大学院・薬学研究科, 助手 (10400269)
堀 里子 東北大学, 大学院・薬学研究科, 助手 (70313145)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2005: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2004: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2003: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2002: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | Blood-brain barrieer / Brain capilary endothelial cells / Transporter / Neural disorders / Regulation / Protection / Energy / Efflux transport / siRNA / 有機アニオン輸送 / 尿毒症 / ABCトランスポーター / Oat / Oatp / 周皮細胞 / 密着結合 / アンジオポエチン / Tie2受容体 / アルツハイマー病 / アミロイド蛋白 / 有機アニオン輸送系 / アルパラギン酸輸送 / 立体選択性 / ASCT / organic anion transporter3(OAT3) / 酸化的ストレス / system Xc^- / system A / クレアチン輸送系 / 脳内エネルギー蓄積物質 / basic FGF |
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| Research Abstract |
The purpose of the project was to clarify the physiological function of transporters at the blood-brain barrier (BBB) relating to neural disorders. The BBB is involved in the brain-to-blood efflux transport of γ-aminobutyric acid, and GAT2/BGT-1 mediates this transport process. BCECs also express serotonin and norepinephrine transporters. Organic anion transporter 3 (OAT3) and ASCT2 are localized at the abluminal membrane of the BCECs. OAT3 is involved in the brain-to-blood efflux of a dopamine metabolite, a uremic toxin and thiopurine nucleobase analogs. ASCT2 plays a role in L-isomer-selective aspartic acid efflux transport at the BBB. Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to-blood efflux transport mediated by organic anion transporting polypeptide 2 and ATA2, respectively. The BBB transporters are regulated by various factors, ATA2 by osmolarity, taurine transporter by TNF-α, and L-cystine/L-glutamic acid exchange transporter by oxidative stress. These results gave us new understanding of the relationship between CNS disorders and BBB function.
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