Huang R, Hertz L
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
J Neurosci Res. 1995 Aug 1;41(5):677-83. doi: 10.1002/jnr.490410514.
Effects of noradrenaline and of adrenergic subtype specific agonists on the uptake and metabolism of [14C]glutamine and [14C]glutamate in primary cultures of mouse astrocytes have been investigated. The total uptake of radioactivity from extracellular [14C]glutamine into the cells was enhanced during exposure to 100 microM noradrenaline, isoproterenol, or clonidine. This is partly due to an increased radioactivity in the glutamine pool and partly due to an increased formation of labeled glutamate from glutamine, which had become very marked (66%) after 240 min of incubation. The CO2 formation from labeled glutamine during 4 hr of incubation was enhanced about twofold in the presence of noradrenaline. Ten millimolar amino oxyacetic acid (AOAA), a transamination inhibitor, had no effect on CO2 formation from glutamine, indicating that the formation of alpha-ketoglutarate from glutamate occurs as an oxidative deamination. The stimulation of 14CO2 production from labeled glutamine was at least as large when glucose was deleted from medium, suggesting that the increased 14CO2 formation represents a stimulation of glutamine metabolism as such and is not only a reflection of an increase in oxidative metabolism of glucose and a bidirectional exchange between alpha-ketoglutarate and glutamate. The opposite process, incorporation of radioactivity from labeled glutamate into glutamine, was not enhanced in the presence of noradrenaline. The findings suggest that noradrenaline stimulates the rates of glutamine uptake, glutamate synthesis, and CO2 production from glutamine and thus increases energy supply to astrocytes but has no effect on the opposite reaction, i.e., glutamine formation from glutamate, a reaction of importance for neuronal-astrocyte interations.
研究了去甲肾上腺素和肾上腺素能亚型特异性激动剂对原代培养的小鼠星形胶质细胞中[14C]谷氨酰胺和[14C]谷氨酸摄取及代谢的影响。在暴露于100微摩尔/升的去甲肾上腺素、异丙肾上腺素或可乐定期间，细胞从细胞外[14C]谷氨酰胺中摄取的总放射性增强。这部分是由于谷氨酰胺池中的放射性增加，部分是由于从谷氨酰胺形成标记谷氨酸的增加，孵育240分钟后这种增加变得非常显著（66%）。在去甲肾上腺素存在的情况下，孵育4小时期间标记谷氨酰胺产生的CO2增加了约两倍。10毫摩尔/升的氨基氧乙酸（AOAA），一种转氨抑制剂，对谷氨酰胺产生CO2没有影响，表明从谷氨酸形成α-酮戊二酸是通过氧化脱氨发生的。当培养基中去除葡萄糖时，标记谷氨酰胺产生14CO2的刺激至少同样大，这表明14CO2形成的增加代表了谷氨酰胺代谢本身的刺激，而不仅仅是葡萄糖氧化代谢增加以及α-酮戊二酸和谷氨酸之间双向交换的反映。相反的过程，即标记谷氨酸中的放射性掺入谷氨酰胺，在去甲肾上腺素存在的情况下没有增强。这些发现表明，去甲肾上腺素刺激谷氨酰胺摄取、谷氨酸合成以及谷氨酰胺产生CO2的速率，从而增加向星形胶质细胞的能量供应，但对相反的反应，即从谷氨酸形成谷氨酰胺没有影响，这一反应对神经元-星形胶质细胞相互作用很重要。
