Abe K, Saito H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.
J Neurochem. 2001 Jan;76(1):217-23. doi: 10.1046/j.1471-4159.2001.00062.x.
The mitogen-activated protein kinases (MAPKs) play a pivotal role in the mediation of cellular responses to a variety of signalling molecules. In the present study, we investigated possible linkage between glutamate signalling and the MAPK cascade in cultured rat cortical astrocytes. Exposure of the cells to L-glutamate (100-1000 microM) resulted in an increase in phosphorylated p44/42 MAPK (ERK1/2) in a concentration- and time-dependent manner. The glutamate-induced ERK1/2 phosphorylation was blocked by U0126 and PD98059, specific inhibitors of the MAPK-activating enzyme MEK. Furthermore, L-glutamate-induced ERK1/2 phosphorylation was not mimicked by glutamate receptor agonists and was not blocked by glutamate receptor antagonists. In contrast, the effect of L-glutamate was mimicked by D- and L-aspartate and transportable glutamate uptake inhibitors. These results suggest that the MEK/ERK cascade is activated by a mechanism related to glutamate transporters. We propose that the glutamate transporter functions as a receptor transmitting extracellular glutamate signal to intracellular messengers.
丝裂原活化蛋白激酶（MAPKs）在介导细胞对多种信号分子的反应中起关键作用。在本研究中，我们调查了培养的大鼠皮质星形胶质细胞中谷氨酸信号与MAPK级联反应之间可能的联系。将细胞暴露于L-谷氨酸（100 - 1000微摩尔）会导致磷酸化的p44/42 MAPK（ERK1/2）以浓度和时间依赖性方式增加。谷氨酸诱导的ERK1/2磷酸化被MAPK激活酶MEK的特异性抑制剂U0126和PD98059阻断。此外，谷氨酸受体激动剂不能模拟L-谷氨酸诱导的ERK1/2磷酸化，谷氨酸受体拮抗剂也不能阻断该过程。相反，D-天冬氨酸和L-天冬氨酸以及可转运的谷氨酸摄取抑制剂能模拟L-谷氨酸的作用。这些结果表明，MEK/ERK级联反应是通过与谷氨酸转运体相关的机制被激活的。我们提出，谷氨酸转运体起到了将细胞外谷氨酸信号传递给细胞内信使的受体的作用。
