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首页> 外文期刊>Journal of pharmaceutical sciences. >Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers.
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Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers.

机译：大鼠质膜单胺转运蛋白在血脑屏障和脑脊液屏障中的功能表征。

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This study investigated the expression and functional roles of rat plasma membrane monoamine transporter (rPMAT) in the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier by using in vitro brain barrier model cells (TR-BBB13 and TR-CSFB3 cells) and multiple in vivo experimental techniques. Quantitative reverse transcription-polymerase chain reaction analysis showed relatively high expression of rPMAT mRNA in TR-BBB13 and TR-CSFB3 cells. 1-Methyl-4-phenylpyridinium (MPP(+) ) was transported into rPMAT-expressing cells in a sodium-independent manner. [(3) H]MPP(+) was taken up concentration dependently by TR-BBB13 and TR-CSFB3 cells with K(m) values similar to that of rPMAT-expressing cells. [(3) H]MPP(+) transports into these cells were markedly inhibited by serotonin, dopamine, and cationic drugs. rPMAT small interfering RNA (siRNA) significantly suppressed the [(3) H]MPP(+) uptake by TR-BBB13 cells. Intracerebrally injected [(3) H]MPP(+) was eliminated from the brain parenchymal region, whereas brain [(3) H]MPP(+) uptake did not increase with time during in situ brain perfusion, suggesting that the brain-to-blood transport across the BBB predominates over the blood-to-brain transport. Brain microdialysis studies revealed that the elimination across the BBB was significantly decreased by coperfusion of unlabelled MPP(+) , serotonin, or dopamine. [(3) H]MPP(+) was also eliminated from the CSF. These findings suggest that PMAT in brain barriers functions as the brain-to-blood transporter to regulate brain concentrations of organic cations including monoamines and cationic neurotoxins.
机译：本研究使用体外脑屏障模型细胞（TR-BBB13和TR-CSFB3细胞）研究了大鼠质膜单胺转运蛋白（rPMAT）在血脑屏障（BBB）和血脑脊液屏障中的表达和功能作用）和多种体内实验技术。定量逆转录-聚合酶链反应分析显示，rPMAT mRNA在TR-BBB13和TR-CSFB3细胞中表达较高。 1-甲基-4-苯基吡啶鎓（MPP（+））以与钠无关的方式转运到表达rPMAT的细胞中。 [（3）H] MPP（+）被TR-BBB13和TR-CSFB3细胞吸收，其K（m）值与表达rPMAT的细胞相似。 [（3）H] MPP（+）转运到这些细胞被血清素，多巴胺和阳离子药物显着抑制。 rPMAT小干扰RNA（siRNA）显着抑制TR-BBB13细胞摄取的[（3）H] MPP（+）。脑内实质区域消除了脑内注射的[（3）H] MPP（+），而在原位脑灌注过程中，脑[[3）H] MPP（+）的摄取并未随时间增加。通过血脑屏障的血液运输占主导地位。脑微透析研究表明，未标记的MPP（+），血清素或多巴胺的共灌注显着降低了血脑屏障的消除。 [（3）H] MPP（+）也从脑脊液中消除。这些发现表明，脑屏障中的PMAT可作为脑到血的转运蛋白，调节大脑中包括单胺和阳离子神经毒素在内的有机阳离子的浓度。

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