Possible linkage between glutamate transporter and mitogen‐activated protein kinase cascade in cultured rat cortical astrocytes

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Abstract
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 µm) 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.