Nitric oxide-induced blockade of NMDA receptors.
We studied the effects of nitric oxide (NO)-producing agents on N-methyl-D-aspartate (NMDA) receptor activation in cultured neurons. 3-Morpholino-sydnonimine (SIN-1) blocked both NMDA-induced currents and the associated increase in intracellular Ca2+. The actions of SIN-1 were reversible and suppressed by hemoglobin. A degraded SIN-1 solution that did not release NO was unable to block NMDA receptors. This showed that the SIN-1 effects were due to NO and not to another breakdown product. Similar results were obtained with 1-nitrosopyrrolidine (an NO-containing drug) and with NO released from NaNO2. Pretreatment with hemoglobin potentiated NMDA-induced effects, demonstrating that endogenous NO modulates NMDA receptors. Since NMDA receptor activation induces NO synthesis, these results suggest a feedback inhibition of NMDA receptors by NO under physiological condition.
Manzoni
O
O
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Prezeau
L
L
Marin
P
P
Desagher
S
S
Deshager
S
S
Bockaert
J
J
Fagni
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009242:N-Nitrosopyrrolidine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012977:Sodium Nitrite / Q000494:pharmacology
D009603:Nitroso Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C002385:linsidomine; D016202:N-Methylaspartate; D008981:Molsidomine; D006152:Cyclic GMP; D012977:Sodium Nitrite; D002118:Calcium; D009242:N-Nitrosopyrrolidine