Gegelashvili G, Schousboe A
PharmaBiotec Research Center, Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.
Brain Res Bull. 1998;45(3):233-8. doi: 10.1016/s0361-9230(97)00417-6.
L-glutamic acid is a key chemical transmitter of excitatory signals in the nervous system. The termination of glutamatergic transmission occurs via uptake of glutamate by a family of high-affinity glutamate transporters that utilize the Na+/K+ electrochemical gradient as a driving force. The stoichiometry of a single translocation cycle is still debatable, although all proposed models stipulate an inward movement of a net positive charge. This electrogenic mechanism is capable of translocating the neurotransmitter against its several thousand-fold concentration gradient, therefore, keeping the resting glutamate concentration below the treshold levels. The five cloned transporters (GLAST/EAAT1, GLT1/EAAT2, EAAC1/EAAT3, EAAT4, and EAAT5) exhibit distinct distribution patterns and kinetic properties in different brain regions, cell types, and reconstitution systems. Moreover, distinct pharmacological profiles were revealed among the species homologues. GLAST and GLT1, the predominant glutamate transporters in the brain, are coexpressed in astroglial processes, whereas neuronal carriers are mainly located in the dendrosomatic compartment. Some of these carrier proteins may possess signal transducing properties, distinct from their transporter activity. Some experimental conditions and several naturally occurring and synthetic compounds are capable of regulating the expression of glutamate transporters. However, selective pharmacological tools interfering with the individual glutamate carriers have yet to be developed.
L-谷氨酸是神经系统中兴奋性信号的关键化学递质。谷氨酸能传递的终止是通过一类高亲和力谷氨酸转运体摄取谷氨酸来实现的，这些转运体利用Na+/K+电化学梯度作为驱动力。尽管所有提出的模型都规定净正电荷向内移动，但单个转运循环的化学计量仍存在争议。这种生电机制能够逆着数千倍的浓度梯度转运神经递质，因此，使静息谷氨酸浓度保持在阈值水平以下。五个已克隆的转运体（GLAST/EAAT1、GLT1/EAAT2、EAAC1/EAAT3、EAAT4和EAAT5）在不同脑区、细胞类型和重组系统中表现出不同的分布模式和动力学特性。此外，在物种同源物中也发现了不同的药理学特征。GLAST和GLT1是脑中主要的谷氨酸转运体，它们在星形胶质细胞突起中共表达，而神经元载体主要位于树突体区室。其中一些载体蛋白可能具有与其转运体活性不同的信号转导特性。一些实验条件以及几种天然存在的和合成的化合物能够调节谷氨酸转运体的表达。然而，尚未开发出干扰单个谷氨酸载体的选择性药理学工具。
