Inhibition of Glutamate Uptake and Proton Pumping in Synaptic Vesicles by S-Nitrosylation |
| |
Authors: | Herman Wolosker Marcelo Reis Jamil Assreuy Leopoldo de Meis |
| |
Affiliation: | Departamentos de Bioquímica Médica and de; Farmacologia, Instituto de Ciencias Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil |
| |
Abstract: | 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. |
| |
Keywords: | Nitric oxide Synaptic vesicles Glutamate Neurotransmitter uptake V-ATPase H+-ATPase |
|
|