2001 Fiscal Year Final Research Report Summary
Development of new drug screening system using the blood-brain barrier transporter gene expression
| Project/Area Number |
12557215
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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 | 展開研究 |
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| Research Field |
医薬分子機能学
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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) |
MORI Shinobu Tohoku University, Graduate School of Pharmaceutical Sciences, Graduate Student, 特別研究員
TAKANAGA Hitomi Tohoku University, Graduate School of Pharmaceutical Sciences, Research Instructor, 大学院・薬学研究科, 助手 (20284523)
OHTSUKI Sumio Tohoku University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 講師 (60323036)
HOSOYA Ken-ichi Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70301033)
ABE Takaaki Tohoku University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (80292209)
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| Project Period (FY) |
2000 – 2001
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| Keywords | blood-brain barrier / plasma membrane / gene expression / culture cell / conditionally immortalized cell line / brain capillary endothelial cells / drug screening / membrane transporter |
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| Research Abstract |
For the development of central nervous system (CNS) acting drug, it is very important subject to have in vitro screening system of the blood-brain barrier transport. We have established the conditionally immortalized cell lines of the brain capillary endothelial cell, astrocyte, pericyte, choroid plexus epithelial cell, retinal endothelial cell, bone marrow derived endothelial cell. Among these cell lines, the brain capillary endothelial cell lines expressed the function of P-glycoprotein, hexose transporter and organic anion transporter. Employing these cell lines, we have revealed the blood-brain barrier transporter gene. We found that ATA2 is responsible gene for the system A, located at the abluminal membrane of the brain capillary endothelial cells. mRNA and transport functio of ATA2 was induced by the hypertonic condition. We have also revealed that TAUT is responsible for the blood-brain barrier transport of taurine. TAUT was induced by hyperosmotic medium condition and cytokine, and reduced by excess cold of taurine. We have also clarified that organic anion transporter 3, OAT3, transport indoxyl sulfate, an uremic toxine, and dehydroepiandrosterone sulfate at the blood-brain barrier in rats. Moreover, we have also revealed that Roct is the mouse counter part of rOAT3. We have also found that the blood-brain barrier CRT play an important role of the uptake of creatine from the circulating blood to the brain. These findings would be very useful for the development of the CNS acting new drug.
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Research Products
(13 results)
