(1S,3R)-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID ATTENUATES N-METHYL-D-ASPARTATE-INDUCED NEURONAL CELL-DEATH IN CORTICAL CULTURES VIA A REDUCTION IN DELAYED CA2+ ACCUMULATION

The effects of (IS,3R)-ACPD, a selective metabotropic glutamate recept or agonist, on NMDA-induced Ca-45(2+) accumulation and delayed neurona l cell death were determined using primary cerebrocortical cultures. E xposure to (IS,3R)-ACPD alone, although causing small increases in Ca- 45(2+) accumulation, was not neurotoxic. The presence of(1S,SR)-ACPD d uring exposure to NMDA attenuated the resulting sustained accumulation of Ca-45(2+) and delayed neuronal cell death. Reductions in sustained Ca2+ accumulation were associated both with Ca2+ efflux, in the absen ce of cell death, and inhibition of delayed intracellular Ca2+ accumul ation. The protective effects of(1S,3R)-ACPD on NMDA-induced cell deat h were inhibited by pretreatment of cultures with pertussis toxin. The se results suggest that activation of metabotropic glutamate receptors may stimulate intracellular processes capable of limiting sustained e levations in intracellular calcium and the resulting excitotoxic neuro nal damage.