Inhibition of glutamate-induced cell death by sodium nitroprusside is not mediated by nitric oxide.

Pretreatment of primary cultures of cerebellar granule cells with sodium nitroprusside (SNP) protected these neurons from delayed death induced by glutamate and N-methyl-D-aspartate (NMDA). This neuroprotective effect was not mimicked by S-nitroso-N-acetylpenicillamine (SNAP) which like SNP stimulates guanylate cyclase via a nitric oxide (NO) related mechanism. In contrast, neuroprotection was achieved with potassium ferrocyanide, a compound structurally related to SNP, but devoid of NO. On the other hand, kainate-induced neurotoxicity was not protected but potentiated by SNP. This effect of SNP was not mimicked by SNAP, potassium ferrocyanide and potassium ferricyanide. We conclude that neuroprotective properties of SNP on glutamate- and NMDA-induced neurotoxicity are not due to the release of NO and activation of guanylate cyclase, but are determined by the ferrocyanide portion of the SNP molecule.