The effects of ebselen on [3H]glutamate uptake by synaptic vesicles from rat brain

Ebselen is a selenium organic compound, which has been shown to be a neuroprotective agent in brain disorders involving glutamate receptors. However, the effects of ebselen on the functionality of the glutamatergic system are still poorly investigated. In this study, by using synaptic vesicle preparation, we investigated the effects of ebselen (0.3 to 10 μM) on (i) vesicular glutamate uptake, (ii) bafilomycin-sensitive H+-ATPase activity, and (iii) proton gradient formation (ΔpH). Ebselen presented a dual effect on glutamate uptake: the 1 μM concentration resulted in a 60% increase of the uptake, while the 10 μM concentration resulted in 60% inhibition. We also observed that ebselen (10 μM) inhibited the H+-ATPase activity and dissipated the ΔpH. The inhibitory effects of ebselen were prevented by dithiothreitol (DTT). These findings suggest that high concentrations of ebselen may oxidize the essential thiol groups of the H+-ATPase, which in turn affect its activity and compromise the vesicular glutamate uptake, and consequently lead to an impairment of the neural homeostasis. [Copyright &y& Elsevier]