Inhibition of Glutamate Uptake and Proton Pumping in Synaptic Vesicles by S-Nitrosylation
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 66, Issue 5, pages 1943–1948, May 1996
How to Cite
Wolosker, H., Reis, M., Assreuy, J. and De Meis, L. (1996), Inhibition of Glutamate Uptake and Proton Pumping in Synaptic Vesicles by S-Nitrosylation. Journal of Neurochemistry, 66: 1943–1948. doi: 10.1046/j.1471-4159.1996.66051943.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received October 31, 1995; revised manuscript received December 21, 1995; accepted December 21, 1995.
- Nitric oxide;
- Synaptic vesicles;
- Neurotransmitter uptake;
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 µM) 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 mM 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.