EVIDENCE AGAINST A PERMISSIVE ROLE OF THE METABOTROPIC GLUTAMATE-RECEPTOR-1 IN ACUTE EXCITOTOXICITY

Excitotoxicity has been proposed to contribute to neuronal loss in a b road spectrum of neurodegenerative conditions such as ischemia, hypogl ycaemic coma or cerebral trauma.(32) Excitotoxic neuronal injury appea rs to be mediated mainly by the over-activation of glutamate receptors , especially N-methyl-D-aspartate receptors, with subsequent excessive Ca2+ influx.(8) Concurrent with the activation of glutamate-gated ion channels, metabotropic glutamate receptors (mGluR), which are G-prote in coupled receptors, are also expected to be activated. Excessive sti mulation of phospholipase C-coupled mGluR, mGluR1 and mGluR5, has been suggested to have neurotoxic consequences.(27) However, the contribut ion of mGluR activation on excitotoxicity is still unclear and controv ersial.(23) Here we report that, following ischemic and excitotoxic br ain injuries, inactivation of mGluR1 does not prevent excitotoxic neur onal damage. Given the evidence that agonists at this group of mGluR p romoted neuronal death in cerebrocortical cultures after oxygen-glucos e deprivation or after N-methyl-D-aspartate exposure,(4,6) our finding s suggest that mGluR-mediated excitotoxicity is unlikely associated wi th mGluR1 but rather with other PLC-coupled mGluR. (C) 1997 IBRO.