Stimulation of Synaptosomal γ‐Aminobutyric Acid Synthesis by Glutamate and Glutamine

Stimulation of Synaptosomal γ‐Aminobutyric Acid Synthesis by Glutamate and Glutamine
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谷氨酸和谷氨酰胺刺激突触体 γ-氨基丁酸合成

DOI:
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发表时间:
1990
期刊:
影响因子:
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通讯作者:
D. L. Martin
D. L. Martin
中科院分区:
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文献类型:
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作者:
G. Battaglioli;D. L. Martin

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通过测量GABA-转氨酶抑制剂gabaculine存在下GABA水平的增加,研究了大鼠脑突触体中的γ-氨基丁酸(GABA)合成。含葡萄糖培养基中突触体GABA合成的基础速率(25.9 nmol/h/mg蛋白)仅为谷氨酸脱羧酶(GAD; 804 ± 83 nmol/h/mg蛋白)最大活性的3%,结果表明突触体GAD仅以其催化能力的一小部分发挥作用。添加500 μ M谷氨酰胺可刺激突触体GABA合成3倍以上。谷氨酸也刺激GABA的合成,但效果较小(1.5倍)。这些结果表明,突触体GAD是不饱和的内源性水平的底物,谷氨酸,并占未使用的催化能力的一部分。谷氨酰胺对GABA合成的更大刺激表明含GAD的隔室比谷氨酸更容易接近突触体外谷氨酰胺。谷氨酰胺的强烈刺激还表明,谷氨酰胺的摄取速率及其转化为谷氨酸的速率可以足够快,以支持神经末梢中的GABA合成。突触体在含葡萄糖的培养基中进行缓慢的天冬氨酸净合成(7.7 nmol/h/mg蛋白质)。谷氨酸和谷氨酰胺强烈刺激天冬氨酸合成,但在这种情况下,谷氨酸的刺激更大。因此,突触体天冬氨酸合成的大部分发生在不同的隔室比GABA合成。
γ‐Aminobutyric acid (GABA) synthesis was studied in rat brain synaptosomes by measuring the increase of GABA level in the presence of the GABA‐transaminase inhibitor gabaculine. The basal rate of synaptosomal GABA synthesis in glucose‐containing medium (25.9 nmol/h/mg of protein) was only 3% of the maximal activity of glutamate decarboxylase (GAD; 804 ± 83 nmol/h/mg of protein), a result indicating that synaptosomal GAD operates at only a small fraction of its catalytic capacity. Synaptosomal GABA synthesis was stimulated more than threefold by adding 500 μM glutamine. Glutamate also stimulated GABA synthesis, but the effect was smaller (1.5‐fold). These results indicate that synaptosomal GAD is not saturated by endogenous levels of its substrate, glutamate, and account for part of the unused catalytic capacity. The greater stimulation of GABA synthesis by glutamine indicates that the GAD‐containing compartment is more accessible to extrasynaptosomal glutamine than glutamate. The strong stimulation by glutamine also shows that the rates of uptake of glutamine and its conversion to glutamate can be sufficiently rapid to support GABA synthesis in nerve terminals. Synaptosomes carried out a slow net synthesis of aspartate in glucose‐containing medium (7.7 nmol/h/mg of protein). Aspartate synthesis was strongly stimulated by glutamate and glutamine, but in this case the stimulation by glutamate was greater. Thus, the larger part of synaptosomal aspartate synthesis occurs in a different compartment than does GABA synthesis.
DOI: 10.1016/0006-2952(85)90207-2
发表时间: 1985-12
影响因子: 5.8
作者:
T. Porter;D. Martin
通讯作者: T. Porter;D. Martin