2010 Fiscal Year Final Research Report
Development of quantitative evaluation method of the drug transport systems at the blood brain barrier which influences the CNS effect.
| Project/Area Number |
20390046
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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 |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUSUHARA Hiroyuki The University of Tokyo, 大学院・薬学系研究科, 准教授 (00302612)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Kazuya 東京大学, 大学院・薬学系研究科, 助教 (00345258)
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| Co-Investigator(Renkei-kenkyūsha) |
WATANABE Yasuyosi 理化学研究所, 分子イメージング科学研究センター, センター長 (40144399)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 薬学 / 薬剤反応性 / 脳・神経 / 血液脳関門 / トランスポーター / 分子イメージング |
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| Research Abstract |
This study focused on the drug transporters expressed in the blood-brain barrier, and aimed at developing quantitative evaluation method of the impact of such drug transporters. In vivo studies using knockout mice elucidated that drugs that are actively extruded by ABC transporters, Mrp4, P-gp and Bcrp at the blood-brain barrier, and thereby, showing limited penetration into the central nervous system. This study also elucidated drugs that are removed by Oat3 from the central nervous system. In conjunction with Mrp4, Oat3 forms efficient directional transport across the blood-brain barrier. This study also found some transporter substrates applicable to PET study.
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Research Products
(46 results)
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[Journal Article] Positron emission tomography studies using (15R)-16-m-[11C]tolyl-17, 18, 19, 20-tetranorisocarbacyclin methyl ester for the evaluation of hepatobiliary transport.2010
Author(s)
Takashima T, Nagata H, Nakae T, Cui Y, Wada Y, Kitamura S, Doi H, Suzuki M, Maeda K, Kusuhara H, Sugiyama Y, Watanabe Y.
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Journal Title
J Pharmacol Exp Ther. 335
Pages: 314-323
Peer Reviewed
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[Journal Article] The ATP-binding cassette transporter BCRP1/ABCG2 plays a pivotal role in cardiac repair after myocardial infarction via modulation of microvascular endothelial cell survival and function.2010
Author(s)
Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Sahara M, Tanaka K, Koibuchi N, Ito S, Kusuhara H, Sugiyama Y, Hirata Y, Nagai R, Sata M.
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Journal Title
Arterioscler Thromb Vasc Biol. 30
Pages: 2128-2135
Peer Reviewed
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[Journal Article] Limited brain distribution of [3R, 4R, 5S]-4-acetamido -5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4).2009
Author(s)
Ose A, Ito M, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M, Hosokawa M, Schuetz JD, Sugiyama Y.
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Journal Title
Drug Metab Dispos 37
Pages: 315-321
Peer Reviewed
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