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Inhibition of Glutamate Uptake and Proton Pumping in Synaptic Vesicles by <i>S</i>‐Nitrosylation
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1996
Year
Nitric OxideSynaptic TransmissionNo •NeurotransmitterNeurotransmissionSynaptic SignalingRedox BiologySocial SciencesOxidative StressMolecular PharmacologyReactive Nitrogen SpecieSynaptic VesiclesSynaptic PhysiologyNeurochemistryBiophysicsBiochemistryNeurotransmitter ReceptorsNeuropharmacologyNeuroprotectionPharmacologyInhibitory NeurotransmittersSynaptic PlasticityNeurophysiologyCellular NeurosciencePhysiologyNeuroscienceMolecular NeurobiologyProton PumpingMedicineGlutamate UptakeNitrosative Stress
Abstract: Nitric oxide (NO; including NO • , NO + , and NO − ) was found to inhibit glutamate uptake by isolated synaptic vesicles of rat brain. This was observed when two unrelated NO donors, S ‐nitrosogluthathione and S ‐nitroso‐ N ‐acetylpenicillamine, were used. The primary target of NO is the H + ‐ATPase found in the synaptic vesicles, which leads to dissipation of the electrochemical proton gradient and inhibition of glutamate uptake. Oxyhemoglobin (12 µ M ) and, to a much lesser extent, methemoglobin protected the vacuolar H + ‐ATPase from inhibition. Inhibition of H + pumping by NO was reversed by addition of 0.5 m M dithiothreitol. The results indicate that the vacuolar H + ‐ATPase from synaptic vesicles is inhibited by NO by a mechanism that involves S ‐nitrosylation of critical sulfhydryl groups in the enzyme. The interaction of NO with synaptic vesicles might be of importance for the understanding of the multiple effects of NO in neurotransmission.