Miller S, Cotman C W, Bridges R J
Department of Psychobiology, University of California, Irvine 92717.
J Neurochem. 1992 May;58(5):1967-70. doi: 10.1111/j.1471-4159.1992.tb10078.x.
In this study we have investigated the effect of excitatory amino acids on the activity of glutamine synthetase, a glial-specific enzyme that plays a key role in the regulation of glutamate concentration in the CNS. We found that of L-glutamate, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, kainate, and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), only the metabotropic glutamate receptor agonist trans-ACPD had an effect on glutamine synthetase specific activity in cultures of rat type I cortical astrocytes. Exposure of astrocytes to 1.0 mM trans-ACPD for 24 h resulted in an increase in glutamine synthetase activity to 149 +/- 11% of that in control cultures. This effect was concentration dependent, stereoselective, and blocked by cycloheximide. In addition, the increase in glutamine synthetase activity occurred at lower concentrations of trans-ACPD that did not produce morphological alterations or lysis of the astrocytes as measured by the lactate dehydrogenase content. These findings are consistent with the hypothesis that activation of the metabotropic excitatory amino acid receptor in astrocytes is coupled to the regulation of an enzyme essential to the metabolism and recycling of the excitatory transmitter L-glutamate.
在本研究中，我们研究了兴奋性氨基酸对谷氨酰胺合成酶活性的影响，谷氨酰胺合成酶是一种神经胶质特异性酶，在中枢神经系统中谷氨酸浓度的调节中起关键作用。我们发现，在L-谷氨酸、N-甲基-D-天冬氨酸、α-氨基-3-羟基-5-甲基异恶唑-4-丙酸、海人酸和1-氨基环戊烷-反式-1,3-二羧酸（反式-ACPD）中，只有代谢型谷氨酸受体激动剂反式-ACPD对大鼠I型皮质星形胶质细胞培养物中的谷氨酰胺合成酶比活性有影响。将星形胶质细胞暴露于1.0 mM反式-ACPD 24小时，导致谷氨酰胺合成酶活性增加至对照培养物中活性的149±11%。这种效应具有浓度依赖性、立体选择性，并被环己酰亚胺阻断。此外，谷氨酰胺合成酶活性的增加发生在较低浓度的反式-ACPD下，通过乳酸脱氢酶含量测定，该浓度不会引起星形胶质细胞的形态改变或裂解。这些发现与以下假设一致，即星形胶质细胞中代谢型兴奋性氨基酸受体的激活与兴奋性递质L-谷氨酸代谢和再循环所必需的一种酶的调节相关。
