| Autor: |
Okamura T; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Okada M; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Kikuchi T; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Wakizaka H; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Zhang MR; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2020 Jan; Vol. 40 (1), pp. 116-125. Date of Electronic Publication: 2018 Oct 22. |
| DOI: |
10.1177/0271678X18808399 |
| Abstrakt: |
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-[ 11 C]methylpurine ([ 11 C] 1 ), which enters the brain and is converted into its glutathione conjugate, S -(7-[ 11 C]methylpurin-6-yl)glutathione ([ 11 C] 2 ). In mice of control and knockout of P-glycoprotein/breast cancer resistance protein and multidrug resistance-associated protein 2 ([ Mrp2 ] -/- ), [ 11 C] 2 formed in the brain was rapidly cleared, with no significant difference in efflux rate. In contrast, [ 11 C] 2 formed in the brain of Mrp 1 -/- mice was slowly cleared, whereas [ 11 C] 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 [ 11 C] 2 efflux across cell membranes, but not BBB. Efflux rate of [ 11 C] 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 [ 11 C] 2 efflux from the brain. Mrp1 may contribute to [ 11 C] 2 efflux from brain parenchymal cells, while extracellular [ 11 C] 2 is likely cleared across the BBB, partly by Oat3 and Mrp4. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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