转运体介导的脑脊液中L-谷氨酸清除：室管膜细胞和脉络丛上皮细胞中表达的兴奋性氨基酸转运体可能参与其中。
Transporter-mediated L-glutamate elimination from cerebrospinal fluid: possible involvement of excitatory amino acid transporters expressed in ependymal cells and choroid plexus epithelial cells.
作者信息
Akanuma Shin-ichi, Sakurai Tatsuhiko, Tachikawa Masanori, Kubo Yoshiyuki, Hosoya Ken-ichi
机构信息
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
出版信息
Fluids Barriers CNS. 2015 Apr 29;12:11. doi: 10.1186/s12987-015-0006-x.
BACKGROUND
L-Glutamate (L-Glu) is the major excitatory neurotransmitter in the CNS, and its level in cerebrospinal fluid (CSF) is reported to be increased in neuroexcitatory diseases such as epilepsy. Since L-Glu concentration in the CSF is reported to be lower than that in plasma, it has been proposed that some mechanisms of L-Glu clearance from the CSF operate in the brain. The purpose of this study was to elucidate the major pathway of L-Glu elimination from rat CSF and the transporters responsible.
METHODS
Protein expression and localization of excitatory amino acid transporters were examined by immunohistochemical analysis using specific antibodies. In vivo elimination of L-Glu from rat CSF was evaluated by intracerebroventricular administration. An L-Glu uptake study by using primary-cultured rat ependymal cells and isolated rat choroid plexus was performed to characterize L-Glu transport mechanisms.
RESULTS
An immunohistochemical analysis has shown that excitatory amino acid transporter (EAAT) 1 and EAAT3, which are D-aspartate-sensitive and kainate-insensitive L-Glu transporters, are localized on the CSF-side of rat ependymal cells and choroid plexus epithelial cells, respectively. In contrast, the kainate-sensitive L-Glu transporter, EAAT2, is not expressed in these cells. In vivo L-Glu elimination clearance from the rat CSF (189 μL/(min · rat)) was 23-fold higher than the CSF bulk flow rate, indicating that facilitative process(es) are involved in L-Glu elimination from the CSF. The in vivo [(3)H]L-Glu elimination from the CSF was significantly inhibited by unlabeled L-Glu and D-aspartate, but not kainate. Moreover, unlabeled L-Glu and D-aspartate inhibited [(3)H]L-Glu uptake by rat ependymal cells and choroid plexus epithelial cells, whereas kainate had little effect.
CONCLUSION
It is suggested that EAAT1 in ependymal cells and EAAT3 in choroid plexus epithelial cells participate in L-Glu elimination from the CSF.
背景
L-谷氨酸（L-Glu）是中枢神经系统中的主要兴奋性神经递质，据报道，在癫痫等神经兴奋性疾病中，其脑脊液（CSF）水平会升高。由于据报道脑脊液中L-Glu浓度低于血浆中的浓度，因此有人提出，脑脊液中L-Glu清除的某些机制在大脑中起作用。本研究的目的是阐明大鼠脑脊液中L-Glu消除的主要途径以及相关转运体。
方法
使用特异性抗体通过免疫组织化学分析检测兴奋性氨基酸转运体的蛋白表达和定位。通过脑室内给药评估大鼠脑脊液中L-Glu的体内消除情况。利用原代培养的大鼠室管膜细胞和分离的大鼠脉络丛进行L-Glu摄取研究，以表征L-Glu转运机制。
结果
免疫组织化学分析表明，兴奋性氨基酸转运体（EAAT）1和EAAT3，即对D-天冬氨酸敏感且对海人酸不敏感的L-Glu转运体，分别定位于大鼠室管膜细胞和脉络丛上皮细胞的脑脊液侧。相比之下，对海人酸敏感的L-Glu转运体EAAT2在这些细胞中不表达。大鼠脑脊液中L-Glu的体内消除清除率（189 μL/（min·只大鼠））比脑脊液总体流速高23倍，表明促进过程参与了脑脊液中L-Glu的消除。未标记的L-Glu和D-天冬氨酸可显著抑制脑脊液中[³H]L-Glu的体内消除，但海人酸无此作用。此外，未标记的L-Glu和D-天冬氨酸可抑制大鼠室管膜细胞和脉络丛上皮细胞对[³H]L-Glu的摄取，而海人酸的作用很小。
结论
提示室管膜细胞中的EAAT1和脉络丛上皮细胞中的EAAT3参与了脑脊液中L-Glu的消除。
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