Selective activation of group II mGluRs with LY354740 does not prevent neuronal excitotoxicity

M. Margarita Behrens, Uta Strasser, Valérie Heidinger, Doug Lobner, Shan Ping Yu, John W. McDonald, Michelle Won, Dennis W. Choi

Research output: Contribution to journalArticle

Abstract

Recent reports have suggested a role for group II metabotropic glutamate receptors (mGluRs) in the attenuation of excitotoxicity. Here we examined the effects of the recently available group II agonist (+)-2-Aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) on N-methyl-D-aspartate (NMDA)-induced excitotoxic neuronal death, as well as on hypoxic-ischemic neuronal death both in vitro and in vivo. At concentrations shown to be selective for group II mGluRs expressed in cell lines (0.1-100 nM), LY354740 did not attenuate NMDA-mediated neuronal death in vitro or in vivo. Furthermore, LY354740 did not attenuate oxygen-glucose deprivation-induced neuronal death in vitro or ischemic infarction after transient middle cerebral artery occlusion in rats. In addition, the neuroprotective effect of another group II agonist, (S)-4-carboxy-3-phenylglycine (4C3HPG), which has shown injury attenuating effects both in vitro and in vivo, was not blocked by the group II antagonists (2S)-α-ethylglutamic acid (EGLU), (RS)-α-methyl-4-sulphonophenylglycine (MSPG), or the group III antagonist (S)-α-methyl-3-carboxyphenylalanine (MCPA), suggesting that this neuroprotection may be mediated by other effects such as upon group I mGluRs.

Original languageEnglish (US)
Pages (from-to)1621-1630
Number of pages10
JournalNeuropharmacology
Volume38
Issue number10
DOIs
StatePublished - Oct 1 1999

Keywords

  • Excitotoxicity
  • Glutamate receptors
  • Neuronal death

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Behrens, M. M., Strasser, U., Heidinger, V., Lobner, D., Yu, S. P., McDonald, J. W., Won, M., & Choi, D. W. (1999). Selective activation of group II mGluRs with LY354740 does not prevent neuronal excitotoxicity. Neuropharmacology, 38(10), 1621-1630. https://doi.org/10.1016/S0028-3908(99)00098-2