THE ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS PROTECTS NERVE-CELLS FROM OXIDATIVE STRESS

Metabotropic glutamate receptors (mGluRs) have been implicated in a va riety of cellular responses to glutamic acid. The work described in th is manuscript extends the role of mGluRs to include protection from ox idative stress-induced programmed cell death. Glutamate analogs regula te inositol-1,4,5 triphosphate mass accumulation in accordance with th eir ability to protect cells from oxidative glutamate toxicity, and pr otection appears to take place at the level of glutathione metabolism. Short-term exposure of cells to low concentrations of glutamate desen sitizes cells to a subsequent challenge from glutamate. Glutamate expo sure upregulates the expression of mGluR5 in hippocampal MT-22 cells a nd mGluR1 in cortical primary cultures. Finally, group I mGluR agonist s also protect cells from death programs initiated by glucose starvati on and cystine deprivation.