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Mechanisms of glutathione-conjugate efflux from the brain into blood: Involvement of multiple transporters in the course
https://repo.qst.go.jp/records/49338
https://repo.qst.go.jp/records/49338c485585e-f245-4cae-9d99-c2a2b5135e04
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-12-19 | |||||
| タイトル | ||||||
| タイトル | Mechanisms of glutathione-conjugate efflux from the brain into blood: Involvement of multiple transporters in the course | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Okamura, Toshimitsu
× Okamura, Toshimitsu× Okada, Maki× Kikuchi, Tatsuya× Wakizaka, Hidekatsu× Ming-Rong, Zhang× Okamura, Toshimitsu× Okada, Maki× Kikuchi, Tatsuya× Wakizaka, Hidekatsu× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Accumulation of detrimental glutathione-conjugated metabolites in the brain potentially causes neurological disorders, and must therefore be exported from the brain. However, in vivo mechanisms of glutathione-conjugates efflux from the brain remain unknown. We investigated the involvement of transporters in glutathione-conjugates efflux using 6-bromo-7-[11C]methylpurine ([11C]1), which enters the brain and is converted into its glutathione conjugate, S-(7-[11C]methylpurin-6-yl)glutathione ([11C]2). In mice of control and knockout of P-glycoprotein/breast cancer resistance protein and multidrug resistance-associated protein 2 ([Mrp2]−/−), [11C]2 formed in the brain was rapidly cleared, with no significant difference in efflux rate. In contrast, [11C]2 formed in the brain of Mrp1−/− mice was slowly cleared, whereas [11C]2 microinjected into the brain of control and Mrp1−/− mice was 75% cleared within 60 min, with no significant difference in efflux rate. These suggest that Mrp1 contributes to [11C]2 efflux across cell membranes, but not BBB. Efflux rate of [11C]2 formed in the brain was significantly lower in Mrp4−/− and organic anion transporter 3 (Oat3)−/− mice compared with control mice. In conclusion, Mrp1, Oat3, and Mrp4 mediate [11C]2 efflux from the brain. Mrp1 may contribute to [11C]2 efflux from brain parenchymal cells, while extracellular [11C]2 is likely cleared across the BBB, partly by Oat3 and Mrp4. | |||||
| 書誌情報 |
Journal of Cerebral Blood Flow & Metabolism 巻 40, 号 1, p. 116-125, 発行日 2018-10 |
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| 出版者 | ||||||
| 出版者 | SAGE Publications | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0271-678X | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1177/0271678X18808399 | |||||
