Williams R J, Maus M, Stella N, Glowinski J, Premont J
Chaire de Neuropharmacologie, INSERM U.114, Collège de France, Paris, France.
Neuroscience. 1996 Sep;74(2):461-8. doi: 10.1016/0306-4522(96)00195-9.
Glucose deprivation potentiates the glutamate receptor-evoked release of arachidonic acid from cultured mouse striatal neurons. In this study we investigated whether this potentiation would be modified by the end-products of glycolysis. These enhanced responses were completely reversed by the addition of increasing concentrations of either lactate or pyruvate. This reversal was not due to increased osmolarity as substituting sucrose for lactate or pyruvate did not mimic their effects. In contrast, in the presence of glucose, neither lactate nor pyruvate was effective. Furthermore, these monocarboxylic acids rescued neuronal respiration in the absence of glucose. Inhibiting glycolysis with iodoacetate in the presence of glucose reproduced the potentiated glutamate-evoked release of arachidonic acid observed following glucose deprivation and reduced neuronal respiration to the same extent as that observed in the absence of glucose. All of these effects were overcome by the addition of either lactate or pyruvate. The reversal of the potentiated glutamate-evoked release of arachidonic acid by lactate or pyruvate was inhibited by a specific inhibitor of monocarboxylic acid transport, alpha-cyano-4-hydroxycinnamic acid, suggesting that lactate and pyruvate act intracellularly. Therefore, we propose that the enhanced release of arachidonic acid evoked by glutamate during glucose deprivation results from reduced glycolysis and hence from a depletion of lactate or pyruvate.
葡萄糖剥夺增强了培养的小鼠纹状体神经元中谷氨酸受体诱发的花生四烯酸释放。在本研究中，我们调查了这种增强作用是否会被糖酵解的终产物所改变。添加浓度不断增加的乳酸或丙酮酸可完全逆转这些增强的反应。这种逆转并非由于渗透压增加，因为用蔗糖替代乳酸或丙酮酸并不能模拟它们的作用。相反，在有葡萄糖存在的情况下，乳酸和丙酮酸均无效。此外，这些单羧酸在没有葡萄糖的情况下挽救了神经元呼吸。在有葡萄糖存在的情况下用碘乙酸抑制糖酵解，再现了在葡萄糖剥夺后观察到的谷氨酸诱发的花生四烯酸释放增强的情况，并将神经元呼吸降低到与在没有葡萄糖的情况下观察到的相同程度。添加乳酸或丙酮酸可克服所有这些影响。乳酸或丙酮酸对谷氨酸诱发的花生四烯酸释放增强的逆转作用被单羧酸转运的特异性抑制剂α-氰基-4-羟基肉桂酸所抑制，这表明乳酸和丙酮酸在细胞内起作用。因此，我们提出，在葡萄糖剥夺期间，谷氨酸诱发的花生四烯酸释放增强是由于糖酵解减少，从而导致乳酸或丙酮酸耗竭所致。
