The iron component of sodium nitroprusside blocks NMDA-induced glutamate accumulation and intracellular Ca2+ elevation
These studies were designed to compare the effects of nitric oxide (NO) generating compounds with those of several iron containing, compounds which do not generate NO on glutamate receptor function. Stimulation of primary cultures of cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainate results in the elevation of intracellular calcium ([Ca2+]i) and cGMP and the release of glutamate. The iron containing compounds, sodium nitroprusside (SNP), potassium ferrocyanide (K4Fe(CN)6) and potassium ferricyanide (K3Fe(CN)6) decrease the NMDA-induced release of glutamate. SNP is the only compound of the above 3 agents which generates NO. A non-iron, NO generating compound, S-nitroso-N-acetylpenicillamin (SNAP), has no effect on the NMDA-induced glutamate release. Potassium ferrocyanide (Fe II), but not potassium ferricyanide (Fe III), blocks NMDA-induced cGMP elevations after 3 min exposure times. This contrasts with the NO generating compounds (both SNP and SNAP) which elevate cGMP levels. Furthermore, both potassium ferrocyanide (Fe II) and SNP (Fe II) suppress the elevation of [Ca2+]i induced by NMDA but neither potassium ferricyanide (Fe III) nor SNAP are effective in this regard. These effects are also independent of cyanide as another Fe II compound, ferrous sulfate (FeSO4) is also able to suppress NMDA-induced elevations of [Ca2+]i SNP was unable to suppress kainate receptor functions. Collectively, these results indicate that Fe II, independently of NO, has effects on NMDA receptor function.
Key WordsCyclic GMP kainate potassium ferrocyanide potassium ferricyanide cerebellar granule cells
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- 2.Bourne, H. R., and Nicoll, R. 1993. Molecular machines integrate coincident synaptic signals, Cell/Neuron 72/10 (supple):65–75.Google Scholar
- 12.Kohr, G., Eckardt, S., Luddens, H., Monyer, H., and Seeberg, P. H. 1994. NMDA receptor channels: subunit-specific potentiation by reducing agents, Neuron 2:1031–1040.Google Scholar
- 14.Ujihara, H., Akaike, A., Tamura, Y., Yokota, T., Sasa, M., Kashii, S., and Honda, Y. 1993. Blockade of retinal NMDA receptors by sodium nitroprusside is probably due to nitric oxide formation, Japan J. Pharmacol. 61:375–377.Google Scholar
- 18.Ellison, D. W., Beal, M. F., and Martin, J. B. 1987. Amino acid neurotransmitters in postmortem human brain analyzed by high performance liquid chromatography with electrochemical detection, J. Neurosci. Metho., 19:305–315.Google Scholar
- 23.Lawrence, A. J., and Jarrot, B. 1993. Nitric oxide increases interstitial excitatory amino acid release in the rat dorsomedial medulla oblongata, Neurosci, Lett. 151:126–129.Google Scholar
- 26.Wroblewski, J. T., Kledrowski, L., Raulli, R., and Costa, E. 1992. Role of nitric oxide in signal transduction of glutamate receptors. in. Excitatory amino acids, ed. R. P. Simon, (Thieme Medical Publishers, New York) p. 81–87.Google Scholar