@article{oai:repo.qst.go.jp:00049338,
 author = {Okamura, Toshimitsu and Okada, Maki and Kikuchi, Tatsuya and Wakizaka, Hidekatsu and Ming-Rong, Zhang and Okamura, Toshimitsu and Okada, Maki and Kikuchi, Tatsuya and Wakizaka, Hidekatsu and Ming-Rong, Zhang},
 issue = {1},
 journal = {Journal of Cerebral Blood Flow & Metabolism},
 month = {Oct},
 note = {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.},
 pages = {116--125},
 title = {Mechanisms of glutathione-conjugate efflux from the brain into blood: Involvement of multiple transporters in the course},
 volume = {40},
 year = {2018}
}