GLUTAMINE AND 2-OXOGLUTARATE AS METABOLIC PRECURSORS OF THE TRANSMITTER POOLS OF GLUTAMATE AND GABA - CORRELATION OF REGIONAL UPTAKE BY RAT-BRAIN SYNAPTOSOMES
GLUTAMINE AND 2-OXOGLUTARATE AS METABOLIC PRECURSORS OF THE TRANSMITTER POOLS OF GLUTAMATE AND GABA - CORRELATION OF REGIONAL UPTAKE BY RAT-BRAIN SYNAPTOSOMES
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DOI：
10.1007/bf01000041
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发表时间：
1989-04-01
影响因子：
4.4
通讯作者：
ASH, CW
中科院分区：
文献类型：
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作者：
SHANK, RP;BALDY, WJ;ASH, CW
为了更清楚地定义谷氨酰胺和2-酮戊二酸作为谷氨酸和GABA递质池的代谢前体的作用，我们已经确定了这四种物质以及腺苷和5-羟色胺由来自大鼠大脑12个区域的突触体积累的相对速率。初始运输条件和低底物浓度被用来最大限度地吸收高亲和力系统，除了谷氨酰胺的摄取测定在低和高浓度。由于谷氨酰胺显著增强了2-酮戊二酸的摄取，因此在孵育培养基中加入和不加入谷氨酰胺（0.2 mM）的情况下测定了2-酮戊二酸的摄取。对于每种基质，吸收的区域差异约为2至14倍。摄取动力学的分析表明，区域差异主要是由于运输能力的差异，而不是底物亲和力，至少谷氨酸，GABA，和2-酮戊二酸。对34个相对摄取值进行了相关分析。2-酮戊二酸和谷氨酸之间，谷氨酰胺和谷氨酸之间的强相关性，而这些底物和GABA之间没有强相关性。我们的研究结果支持这样的观点，即谷氨酰胺和2-酮戊二酸是整个大鼠大脑谷氨酸递质池的主要前体，但它们对补充GABA递质池的相对贡献不太确定。
To more clearly define the roles of glutamine and 2-oxoglutarate as metabolic precursors of the transmitter pools of glutamate and GABA we have determined the relative rates at which these four substances, and adenosine and serotonin are accumulated by synaptosomes derived from twelve regions of the rat brain. Initial transport conditions and low substrate concentrations were used to maximize uptake by high-affinity systems, except the uptake of glutamine was determined at both low and high concentrations. Because the uptake of 2-oxoglutarate is markedly enhanced by glutamine, 2-oxoglutarate uptake was determined with and without glutamine (0.2 mM) added to the incubation medium. For each substrate, regional differences in uptake ranged from approximately two- to fourteen-fold. An analysis of uptake kinetics revealed that the regional differences were due primarily to differences in transport capacity rather than substrate affinities, at least for glutamate, GABA, and 2-oxoglutarate. Thirty-four correlation analyses of relative uptake value s were performed. Strong correlations were found between 2-oxoglutarate and glutamate, and between glutamine and glutamate, whereas no strong correlations occurred between these substrates and GABA. Our results support the view that both glutamine and 2-oxoglutarate are major precursors of the transmitter pool of glutamate throughout the rat brain, but their relative contributions toward replenishing the transmitter pool of GABA are less certain.