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Biochem Biophys Res Commun. 2018 Sep 26;504(1):103-108. doi: 10.1016/j.bbrc.2018.08.137. Epub 2018 Aug 28.

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

Author information

1
Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan.
2
Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan. Electronic address: matsuoka2@okayama-u.ac.jp.

Abstract

AIM OF THE RESEARCH:

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.

METHODS:

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.

RESULTS:

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 astrocytes and RNB cells. Furthermore, the effect of norepinephrine was reversed by an α-adrenoceptor antagonist.

CONCLUSION:

Norepinephrine downregulates GLT-1 mRNA expression in astrocytes via the α1-adrenoceptor. Our results provide new insight into the mechanisms involved in downregulation of GLT-1 in the chronic pain models.

KEYWORDS:

Astrocyte; Descending inhibitory pathway; Glutamate transporter; Neuropathic pain; Norepinephrine; Spinal cord

PMID:
30170732
DOI:
10.1016/j.bbrc.2018.08.137
[Indexed for MEDLINE]

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