Interference of S-Nitrosoglutathione with the Binding of Ligands to Ionotropic Glutamate Receptors in Pig Cerebral Cortical Synaptic Membranes |
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Authors: | András Hermann Vince Varga Réka Janáky Róbert Dohovics Pirjo Saransaari Simo S Oja |
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Institution: | (1) Brain Research Center, Medical School, University of Tampere, FIN-33014, Finland;(2) Department of Animal Anatomy and Physiology, University of Debrecen, Box 15, H-4010 Debrecen, Hungary;(3) Department of Animal Anatomy and Physiology, University of Debrecen, Box 15, H-4010 Debrecen, Hungary;(4) Department of Clinical Physiology, Tampere University Hospital, Box 2000, FIN-33521 Tampere, Finland |
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Abstract: | The interactions of S-nitrosoglutathione (GSNO) with the ionotropic glutamate receptors were studied on synaptic membranes isolated from the pig cerebral cortex. GSNO displaced the binding of 3H]glutamate, 3-(R)-2-carboxypiperazin-4-yl]3H]propyl-1-phosphonate (3H]CPP), a competitive N-methyl-D-aspartate (NMDA) antagonist, and 3H]kainate, with IC50 values in the low micromolar range. It failed to displace (S)-5-fluoro-3H]willardiine, a selective agonist of 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Reduced and oxidized glutathione were almost as effective as GSNO in glutamate and CPP binding. Of the three, GSNO was the most potent in kainate binding. They all stimulated 3H]dizocilpine binding in a concentration-dependent manner. This effect was additive to that of glycine and not mimicked by NO donors such as S-nitroso-N-acetylpenicillamine, 5-amino-3-morpholinyl-1,2,3-oxadiazolium chloride (SIN-1) and nitroglycerin. We assume that GSNO may act as an endogenous ligand at the NMDA and non-NMDA classes of glutamate receptors. In this manner it may facilitate NO transfer and target its delivery to specific sites in these receptors. |
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Keywords: | Nitric oxide glutathione S-nitrosoglutathione ionotropic glutamate receptors |
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