Nitric oxide synthase activity endogenously modulates NMDA receptors.
We tested the possibility that endogenous nitric oxide synthase activity regulated NMDA receptors in primary cultured striatal neurons. We monitored NMDA-induced increase in intracellular Ca2+ levels with fura-2 ratio imaging, while nitric oxide synthase activity was either increased with L-arginine (the natural substrate of nitric oxide synthase) or inhibited using nitro-L-arginine (a specific inhibitor of nitric oxide synthase). We found that the NMDA receptor effect was slowly but strongly diminished after an L-arginine (1 mM, 15 min) treatment (L-arginine preincubation reduced the 100 microM NMDA-induced maximal effect by 30-50%). The L-arginine blockade of NMDA receptors was long-lasting but could be partially reversed by hemoglobin (100 microM, 10 min), which binds nitric oxide. This was not observed when the neurons were treated with L-arginine together with nitro-L-arginine. Our data strongly suggest that physiological nitric oxide synthase activity could regulate NMDA receptors.
Manzoni
O
O
CNRS UPR 9023, Montpellier, France.
Bockaert
J
J
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D007425:Intracellular Membranes / Q000378:metabolism; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009994:Osmolar Concentration; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium