2001 Fiscal Year Final Research Report Summary
cDNA cloning of blood-brain barrier neurotransmitter transporter and analysis of its physiological function
| Project/Area Number |
12470522
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Tohoku University |
|---|
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)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | blood-brain barrier / membrane transport / neurotransmitter / organic anion transporter / cDNA cloning / central nervous system detoxification / conditionally immortalized cell line / brain capillary endothelial cell |
|---|
| Research Abstract |
The purpose of the present study is to clarify the neurotransmitter transport mechanism at the blood-brain barrier (BBB). As in vitro BBB model, a conditionally immortalized brain capillary endothelial cell line was used. The Brain Efflux Index (BEI) method was used to determine the in vivo BBB efflux rate in rats. We have clarified that Na^+ dependent stereo-selective aspartic acid transport system was functioning at the BBB. ASCT was suggested for the potential candidate of the L-Asp selective transport in the brain capillary endothelial cells. It was demonstrated that γ-aminobutylic acid (GABA) was transported from the brain to the blood across the BBB. GAT-2/BGT1 was suggested for the responsible transporter protein of GABA at the BBB. Organic anion transporting polypeptide 2 (oatp2) was suggested for the responsible transporter of dehydroepiandrosterone sulfate and estrone-3-sulfate at the BBB. Moreover, we have found that the brain capillary endothelial cells have the serotonine and norepinephrine transpot proteins. These new findings suggested that the BBB would play an important physiological role of rescue system for the central nervous system when there would be excess amount of neuretransmitters in the brain interstitial fluid. This is a quite new finding in the blood-brain barrier research and will significantly stimulate the progress of the future research.
|
