Molecular mechanism of blood-brain barrier transport of drugs.
| Project/Area Number |
09672221
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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 |
Biological pharmacy
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
TAMAI Ikumi Kanazawa University, Graduate School, Associate Professor, 大学院・自然科学研究科, 助教授 (20155237)
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| Co-Investigator(Kenkyū-buntansha) |
SAI Yoshimichi Kanazawa University, Pharmacy, Research Associate, 薬学部, 助手 (40262589)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Blood-brain barrier / transporter / carrier-mediated transport / drug delivery / drug disposition / P-glycoprotein / monocarboxylic acid / beta-amino acid / トランスポート / ドラッグデリバリー / 培養細胞 / 膜輸送 / 脳毛細血管内皮細胞 |
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| Research Abstract |
Various transport systems equipped in brain capillary endothelial cells (BECEC) that form blood-brain barrier (BBB) were characterized as follows :
1.beta-amino acid transport system : beta-amino acids such as beta-alanine and taurine were transported across the blood-brain barrier by specific carrier-mediated transport mechanisms that is energized by sodium ion gradient in a chloride ion sensitive manner. The transporter function was found bcth at the luminal and abluminal membranes of BCEC, indicating that both of influx and efflux of beta-amino acids across the BBB are regulated such transporter(s).
2.Substrate specificity of adsorptive-mediated endocytosis at the BBB was further investigated using primary cultured bovine BCEC.By newly synthesizing cationic-derived peptide with various lipophilicity, isoelectric point and molecular size, the optimal structure for the mechanism was speculated.
3.Molecular characterization of the transporter for monocarboxylic acids such as lactic acid has been performed. Monocarboxylic acid transporter MCT-1 gene was expressed in the BCEC and was found to functionally play important role in transport of organic weak acids at the BBB by the in vitro cultured cells and in vivo BUl studies.
4.Multiple brain efflux mechanisms for new quinolone antibacterial agent, HSR-903 were found to be functionally expressed at the BBB.They are P-glycoprotein and unknown transporter sensitive to anionic compounds. These multiple efflux transporters seem to restrict brain distribution of HSR-903, resulting in a low toxicity in the central nervous system.
These lines of studies provide new insight of the function of BBB and imply new strategy to control brain distribution of drugs by focusing on the transporters functioning at the blood-brain barrier.
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Report
(3 results)
Research Products
(9 results)
