Transport of glutamate and other amino acids at the blood-brain barrier
Transport of glutamate and other amino acids at the blood-brain barrier
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DOI：
10.1093/jn/130.4.1016s
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发表时间：
2000-04-01
影响因子：
4.2
通讯作者：
Smith, QR
中科院分区：
文献类型：
--
作者：
Smith, QR
在大脑的大多数区域，循环中谷氨酸和其他阴离子兴奋性氨基酸的吸收受到血脑屏障(BBB)的限制。在大多数动物中，血脑屏障由脑血管内皮细胞组成，血管内皮细胞由多条紧密连接的细胞连接在一起。这些连接有效地关闭了通过细胞间毛孔的扩散；结果是，大多数溶质要么通过类脂内皮细胞膜扩散，要么通过特定的载体运输穿过血脑屏障。用体外细胞摄取试验和体内灌流方法研究了谷氨酸在血脑屏障的转运。结果表明，在生理血浆浓度下，谷氨酸从血浆进入脑内是由血脑屏障的高亲和力转运系统介导的。从大脑回流到血浆似乎在很大程度上是由毛细血管膜上的钠依赖的主动转运系统驱动的。脑间质液中的谷氨酸浓度只是血浆的一小部分，并且与血浆浓度的微小波动保持相当独立。对几种兴奋性谷氨酸类似物，包括软骨藻酸和犬尿酸，也观察到大脑通路受限。总而言之，血脑屏障是调节系统的一个组成部分，它帮助维持大脑间质液体谷氨酸浓度独立于循环。
In most regions of the brain, the uptake of glutamate and other anionic excitatory amino acids from the circulation is limited by the blood-brain barrier(BBB). In most animals, the BBB is formed by the brain vascular endothelium, which contains cells that are joined by multiple bands of tight junctions. These junctions effectively close off diffusion through intercellular pores; as a result, most solutes cross the BBB either by diffusing across the lipoid endothelial cell membranes or by being transported across by specific carriers. Glutamate transport at the BBB has been studied by both in vitro cell uptake assays and in vivo perfusion methods. The results demonstrate that at physiologic plasma concentrations, glutamate flux from plasma into brain is mediated by a high affinity transport system at the BBB. Efflux from brain back into plasma appears to be driven in large part by a sodium-dependent active transport system at the capillary abluminal membrane. Glutamate concentration in brain interstitial fluid is only a fraction of that of plasma and is maintained fairly independently of small fluctuations in plasma concentration. Restricted brain passage is also observed for several excitatory glutamate analogs, including domoic acid and kynurenic acid. In summary, the BBB is one component of a regulatory system that helps maintain brain interstitial fluid glutamate concentration independently of the circulation.