Napper G A, Kalloniatis M
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
Vis Neurosci. 1999 Nov-Dec;16(6):1169-80. doi: 10.1017/s0952523899166161.
Glutamate and gamma-aminobutyric acid (GABA) are the dominant amino acids in the retina and brain. The manufacturing and degradation pathways of both of these amino acids are intricately linked with the tricarboxylic acid cycle leading to rapid redistribution of these amino acids after metabolic insult. Postmortem ischemia in mammalian retina predominantly results in a loss of glutamate and GABA from neurons and accumulation of these amino acids within Müller cells. This accumulation of glutamate and GABA in Müller cells may occur as a result of increased release of these neurotransmitters from neurons, and decreased degradation. Quantification of the semisaturation value (half-maximal response) for glutamate and GABA Müller cell loading during postmortem ischemia indicated a shorter semisaturation value for GABA than glutamate. Such changes are consistent with a single aerobically dependent GABA-degradation pathway, and the existence of multiple glutamate-degradation pathways. Comparison with the in vitro ischemic model showed similar qualitative characteristics, but a markedly increased semisaturation time for glutamate and GABA Müller cell loading (a factor of 5-10) in the postmortem ischemia model. We interpret these differences to indicate that the in vitro condition provides a more immediate and/or severe ischemic insult. In the postmortem ischemia model, the delayed glial cell loading implies the availability of internal stores of both glucose and/or oxygen. Increased glial and neuronal immunoreactivity for the amino acids involved in transamination reactions, aspartate, alanine, leucine, and ornithine was observed, indicating a potential shift in the equilibrium of transamination reactions associated with glutamate production. These findings provide evidence that, in the rat retina, there are multiple pathways subserving glutamate production/degradation that include a multitude of transamination reactions. Further evidence is therefore provided to support a role for all four amino acids in glutamate metabolism within a variety of retinal neurons and glia.
谷氨酸和γ-氨基丁酸（GABA）是视网膜和大脑中的主要氨基酸。这两种氨基酸的合成和降解途径与三羧酸循环紧密相连，导致在代谢损伤后这些氨基酸迅速重新分布。哺乳动物视网膜的死后缺血主要导致神经元中谷氨酸和GABA的丧失以及这些氨基酸在Müller细胞内的积累。谷氨酸和GABA在Müller细胞中的这种积累可能是由于这些神经递质从神经元的释放增加以及降解减少所致。对死后缺血期间谷氨酸和GABA在Müller细胞内负载的半饱和值（半数最大反应）的定量分析表明，GABA的半饱和值比谷氨酸短。这些变化与单一的需氧依赖性GABA降解途径以及多种谷氨酸降解途径的存在相一致。与体外缺血模型的比较显示出相似的定性特征，但在死后缺血模型中，谷氨酸和GABA在Müller细胞内负载的半饱和时间明显增加（5至10倍）。我们将这些差异解释为表明体外条件提供了更直接和/或更严重的缺血性损伤。在死后缺血模型中，胶质细胞的延迟负载意味着葡萄糖和/或氧气的内部储存是可用的。观察到参与转氨反应的氨基酸天冬氨酸、丙氨酸、亮氨酸和鸟氨酸的胶质细胞和神经元免疫反应性增加，表明与谷氨酸产生相关的转氨反应平衡可能发生了变化。这些发现提供了证据，表明在大鼠视网膜中，存在多种支持谷氨酸合成/降解的途径，其中包括多种转氨反应。因此，进一步的证据支持了这四种氨基酸在多种视网膜神经元和胶质细胞内谷氨酸代谢中的作用。
