pyrimidinones and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

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.

Topics: Alanine; Animals; Binding, Competitive; Cerebral Cortex; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Glutathione; Kainic Acid; Kinetics; Ligands; Neuroprotective Agents; Nitroso Compounds; Piperazines; Pyrimidinones; Receptors, AMPA; Receptors, Glutamate; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; S-Nitrosoglutathione; Swine; Synaptic Membranes; Uracil