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 language | English (US) |
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Pages (from-to) | 1621-1630 |
Number of pages | 10 |
Journal | Neuropharmacology |
Volume | 38 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1999 |
Externally published | Yes |
Keywords
- Excitotoxicity
- Glutamate receptors
- Neuronal death
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience