Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors.

To define the significance of glutamate ionotropic receptors in sPLA 2 -mediated neuronal cell death we used the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist PNQX. In primary neuronal cell cultures both MK-801 and PNQX inhibited sPLA 2 - and glutamate-induced neuronal death. [ 3 H]Arachidonic acid release induced by both sPLA 2 and glutamate was partially blocked by MK-801, indicating that the glutamate-NMDA-cPLA 2 pathway contributes to sPLA 2 -induced arachidonic acid release. Systemic administration of MK-801 to rats that had sPLA 2 injected into the right striatum significantly decreased neuronal cell death. We conclude that glutamatergic synaptic activity modulates sPLA 2 -induced neuronal cell death.