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Metabotropic glutamate receptor agonists reduce glutamate release from cultured astrocytes
Author(s) -
Ye ZuCheng,
Sontheimer Harald
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(19990201)25:3<270::aid-glia7>3.0.co;2-v
Subject(s) - acpd , metabotropic glutamate receptor , glutamate receptor , biology , agonist , metabotropic glutamate receptor 1 , metabotropic receptor , metabotropic glutamate receptor 3 , nmda receptor , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 5 , biophysics , biochemistry , neuroscience , receptor
Astrocytes are thought to control extracellular glutamate concentrations ([Glu] o ) in the brain, thereby protecting neurons from excitotoxic injury. We investigated the effects of metabotropic glutamate receptor (mGluR) agonists on glutamate transport and [Glu] o in primary hippocampal astrocytic cultures. Acute or chronic exposure of astrocytes to the mGluR agonist trans ‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ( trans ‐ACPD) or its active isomer 1 S ,3 R ‐ACPD reduced [Glu] o in a time‐ and dose‐dependent manner (44.5 ± 3.6% reductions of [Glu] o in astrocytes from P0–P10 rats and 65.9 ± 4.1 % from rats P20 by 100 μM 1 S ,3 R ‐ACPD, EC 50 ∼ 5 μM). 1 S ,3 R ‐ACPD effects developed slowly (median effective at ∼60 min) and persisted for several hours after agonist removal. ACPD‐pretreated astrocytes established lower steady‐state [Glu] o levels. ACPD effects persisted in the presence of the glutamate uptake inhibitors D , L ‐threo‐β‐hydroxyaspartate (THA) and L ‐ trans ‐pyrrolidine‐2,4‐dicarboxylate (PDC) but were impaired by disruption of the transmembrane Na + , K + , or H + gradients. In addition, 1 S ,3 R ‐ACPD had no effects on intracellular glutamate content and did not directly block glutamate transport. Furthermore, ACPD effects could be mimicked by glutamate per se and several other compounds presumed to be mGluR agonists, although ( S )‐3,5‐dihydroxyphenylglycine (DHPG), (2 S ,2 R ,3 R )‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV), and L ‐(+)‐2‐amino‐4‐phosphonobutyric acid ( L ‐AP4) were without effect. These data suggest that glutamate and certain mGluR agonists may regulate [Glu] o by modulating the transmembrane equilibrium of glutamate transport, especially by attenuating glutamate release. GLIA 25:270–281, 1999. © 1999 Wiley‐Liss, Inc.