Glutamine from Glial Cells Is Essential for the Maintenance of the Nerve Terminal Pool of Glutamate: Immunogold Evidence from Hippocampal Slice Cultures
Glutamine from Glial Cells Is Essential for the Maintenance of the Nerve Terminal Pool of Glutamate: Immunogold Evidence from Hippocampal Slice Cultures
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胶质细胞中的谷氨酰胺对于维持神经末梢谷氨酸池至关重要：来自海马切片培养物的免疫金证据
DOI：
10.1046/j.1471-4159.1995.65020871.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
O. Ottersen
中科院分区：
文献类型：
--
作者：
Jon Henrik Laake;T. A. Slyngstad;F. Haug;O. Ottersen
摘要：在抑制L-谷氨酰胺合成酶[L-谷氨酸：氨连接酶（ADP-形成）; EC www.example.com ]后，在海马切片培养物中在电子显微镜水平上研究了谷氨酸和谷氨酰胺的免疫金标记6.3.1.2。在对照培养物中，谷氨酸样免疫反应性在终末中最高，在锥体细胞体中居中，在胶质细胞中较低。神经胶质细胞中谷氨酰胺样免疫反应性高，锥体细胞体中中等，终末中低。用l-甲硫氨酸亚砜亚胺抑制谷氨酰胺合成酶后，终末中的谷氨酸样免疫反应性降低了52%，而神经胶质中的谷氨酸样免疫反应性增加了近4倍。L-蛋氨酸亚砜亚胺后，神经胶质中的谷氨酰胺样免疫反应性降低了66%，但在其他隔室中变化不大。在用L-甲硫氨酸亚砜亚胺和谷氨酰胺（1.0 mM）处理的培养物中，终末中的谷氨酸样免疫反应性维持在对照水平，而在神经胶质中，谷氨酸样免疫反应性增加，谷氨酰胺样免疫反应性降低至与单独用L-甲硫氨酸亚砜亚胺处理的培养物相似的程度。我们的结论是：（a）当通过谷氨酰胺合成酶的通量被阻断时，谷氨酸在胶质细胞中积累，强调了这一途径对处理谷氨酸的重要性;（B）谷氨酰胺对于维持末端谷氨酸的正常水平是必要的，并且通过谷氨酰胺酶反应以外的途径的再摄取和从头合成都是不够的。
Abstract: The immunogold labeling for glutamate and glutamine was studied at the electron microscopic level in hippocampal slice cultures following inhibition of l‐glutamine synthetase [l‐glutamate:ammonia ligase (ADP‐forming); EC 6.3.1.2]. In control cultures, glutamate‐like immunoreactivity was highest in terminals, intermediate in pyramidal cell bodies, and low in glial cells. Glutamine‐like immunoreactivity was high in glial cells, intermediate in pyramidal cell bodies, and low in terminals. After inhibition of glutamine synthetase with l‐methionine sulfoximine, glutamate‐like immunoreactivity was reduced by 52% in terminals and increased nearly fourfold in glia. Glutamine‐like immunoreactivity was reduced by 66% in glia following l‐methionine sulfoximine, but changed little in other compartments. In cultures that were treated with both l‐methionine sulfoximine and glutamine (1.0 mM), glutamate‐like immunoreactivity was maintained at control levels in terminals, whereas in glia glutamate‐like immunoreactivity was increased and glutamine‐like immunoreactivity was decreased to a similar extent as in cultures treated with l‐methionine sulfoximine alone. We conclude that (a) glutamate accumulates in glia when the flux through glutamine synthetase is blocked, emphasizing the importance of this pathway for the handling of glutamate; and (b) glutamine is necessary for the maintenance of a normal level of glutamate in terminals, and neither reuptake nor de novo synthesis through pathways other than the glutaminase reaction is sufficient.