Résumé
: We tested the possibility that endogenous nitric oxide synthase activity regulated NMDA receptors in primary cultured striatal neurons. We monitored NMDA‐induced increase in intra‐cellular Ca2+ levels with fura‐2 ratio imaging, while nitric oxide synthase activity was either increased with l‐arginihe (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 μM 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 μM, 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.