Robinson M B
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania 19104-4318, USA.
Neurochem Int. 1998 Dec;33(6):479-91. doi: 10.1016/s0197-0186(98)00055-2.
The acidic amino acids, glutamate and aspartate, are the predominant excitatory neurotransmitters in the mammalian CNS. Under many pathologic conditions, these excitatory amino acids (EAAs) accumulate in the extracellular fluid in CNS and the resultant excessive activation of EAA receptors contributes to brain injury through a process known as 'excitotoxicity'. Unlike many other neurotransmitters, there is no evidence for extracellular metabolism of EAAs, rather, they are cleared by Na+-dependent transport mechanisms. Therefore, this transport process is important for ensuring crisp synaptic signaling as well as limiting the excitotoxic potential of EAAs. With the cloning of five distinct EAA transporters, a variety of tools were developed to characterize individual transporter subtypes, including specific antibodies, expression systems, and probes to delete/knock-down expression of each subtype. These tools are beginning to provide fundamental information that has the potential to impact our understanding of EAA physiology and pathophysiology. For example, biophysical studies of the cloned transporters have led to the observation that some subtypes function as ligand-gated ion channels as well as transporters. With these reagents, it has also been possible to explore the relative contributions of each transporter to the clearance of extracellular EAAs and to begin to examine the regulation of specific transporter subtypes. In this review, an overview of the properties of the transporter subtypes will be presented. The evidence which suggests that the transporter, GLT1/EAAT2, may be sufficient to explain a large percentage of forebrain transport will be critically reviewed. Finally, the studies of regulation of GLT-1 in vitro and in vivo will be described.
酸性氨基酸，谷氨酸和天冬氨酸，是哺乳动物中枢神经系统中主要的兴奋性神经递质。在许多病理条件下，这些兴奋性氨基酸（EAA）在中枢神经系统的细胞外液中积累，EAA受体的过度激活通过一种称为“兴奋毒性”的过程导致脑损伤。与许多其他神经递质不同，没有证据表明EAA在细胞外进行代谢，相反，它们通过钠依赖性转运机制清除。因此，这种转运过程对于确保清晰的突触信号以及限制EAA的兴奋毒性潜力很重要。随着五种不同的EAA转运体的克隆，开发了各种工具来表征各个转运体亚型，包括特异性抗体、表达系统以及用于删除/敲低各亚型表达的探针。这些工具开始提供有可能影响我们对EAA生理学和病理生理学理解的基础信息。例如，对克隆转运体的生物物理研究发现，一些亚型既作为配体门控离子通道又作为转运体发挥作用。利用这些试剂，还能够探究每个转运体对细胞外EAA清除的相对贡献，并开始研究特定转运体亚型的调节。在这篇综述中，将概述转运体亚型的特性。将严格审查表明转运体GLT1/EAAT2可能足以解释大部分前脑转运的证据。最后，将描述GLT-1在体外和体内的调节研究。
