Nitric oxide-induced blockade of NMDA receptors
Neuron, 1992•cell.com
Westudied theeffectsof nitricoxide (NO) groducingagents on N-methyl+-aspartate (NMDA)
receptor activation in cultured neurons. 3-Morpholino-sydnonimine (SIN-l) blocked both
NMDA-induced currents and the associated increase in intracellular Ca*+. The actions of
SIN-l 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 l …
receptor activation in cultured neurons. 3-Morpholino-sydnonimine (SIN-l) blocked both
NMDA-induced currents and the associated increase in intracellular Ca*+. The actions of
SIN-l 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 l …
Summary
Westudied theeffectsof nitricoxide (NO) groducingagents on N-methyl+-aspartate (NMDA) receptor activation in cultured neurons. 3-Morpholino-sydnonimine (SIN-l) blocked both NMDA-induced currents and the associated increase in intracellular Ca*+. The actions of SIN-l 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 l-nitrosopyrrolidine (an NO-containingdrug) and with NO released from NaN02. Pretreatment with he moglobin potentiated NMDA-induced effects, demonstrating that endogenous NO modulates NMDA receptors. Since NMDA receptor activation induces NO synthesis, these re sults suggest a feedback inhibition of NMDA receptors by NO under physiological condition.
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