(1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid attenuates [formula omitted] neuronal cell death in cortical cultures via a reduction in delayed ca 2+ accumulation

Abstract

The effects of (1S,3R)-ACPD, a selective metabotropic glutamate receptor agonist, on NMDA-induced 45Ca 2+ accumulation and delayed neuronal cell death were determined using primary cerebrocortical cultures. Exposure to (1S,3R)-ACPD alone, although causing small increases in 45Ca 2+ accumulation, was not neurotoxic. The presence of (1S,3R)-ACPD during exposure to NMDA attenuated the resulting sustained accumulation of 45Ca 2+ and delayed neuronal cell death. Reductions in sustained Ca 2+ accumulation were associated both with Ca 2+ efflux, in the absence of cell death, and inhibition of delayed intracellular Ca 2+ accumulation. The protective effects of (1S,3R)-ACPD on NMDA-induced cell death were inhibited by pretreatment of cultures with pertussis toxin. These results suggest that activation of metabotropic glutamate receptors may stimulate intracellular processes capable of limiting sustained elevations in intracellular calcium and the resulting excitotoxic neuronal damage.