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

Author:
Kurita, Masako, Matsuoka, Yoshikazu, Nakatsuka, Kosuke, Ono, Daisuke, Muto, Noriko, Kaku, Ryuji, Morimatsu, Hiroshi
Source:
Biochemical and biophysical research communications 2018 v.504 no.1 pp. 103-108
ISSN:
0006-291X
Subject:
agonists, alpha-1 adrenergic receptors, amino acid transporters, antagonists, astrocytes, cell lines, dosage, gene expression, gene expression regulation, homeostasis, in vitro studies, messenger RNA, models, nerve tissue, norepinephrine, pain, phenylephrine, quantitative polymerase chain reaction, rats, reverse transcriptase polymerase chain reaction, spinal cord
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 astrocytes and RNB cells. Furthermore, the effect of norepinephrine was reversed by an α-adrenoceptor antagonist.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.
Agid:
6153529