Norepinephrine-induced downregulation of GLT-1 mRNA in rat astrocytes

Biochemical and Biophysical Research Communications
Masako KuritaHiroshi Morimatsu

Abstract

Glutamate transporter-1 (GLT-1; also known as excitatory amino acid transporter 2) plays an important role in the maintenance of glutamate homeostasis in the synaptic cleft. Downregulation of GLT-1 in the spinal cord has been reported in chronic pain models, which suggests that GLT-1 is involved in the development of chronic pain. However, the mechanism by which GLT-1 is downregulated in the spinal cord is still unknown. We hypothesized that norepinephrine is involved in the regulation of GLT-1. The aim of this study was to investigate the effect of norepinephrine on GLT-1 expression in cultured astrocytes. This study involved both in vivo and in vitro experiments. We first validated changes in GLT-1 mRNA expression in the spinal cord of rats with spared nerve injury (SNI) using real-time RT-PCR. Next, cultured primary astrocytes from the rat spinal cord were stimulated with norepinephrine, and GLT-1 mRNA was subsequently quantitated. RNB cells, an astrocytic cell line, were also stimulated with norepinephrine and other α-adrenoceptor agonists. SNI resulted in bilateral downregulation of GLT-1 in rat spinal cord. The in vitro study showed that norepinephrine and phenylephrine dose-dependently downregulated GLT-1 in primary astr...Continue Reading

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