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 microM) on (i) vesicular glutamate uptake, (ii) bafilomycin-sensitive H+ -ATPase activity, and (iii) proton gradient formation (DeltapH). Ebselen presented a dual effect on glutamate uptake: the 1 microM concentration resulted in a 60% increase of the uptake, while the 10 microM concentration resulted in 60% inhibition. We also observed that ebselen (10 microM) inhibited the H+ -ATPase activity and dissipated the DeltapH. 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.
Porciúncula
Lisiane O
LO
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre/RS, 90035 003, Brazil. loporciuncula@yahoo.com
Rocha
João Batista T
JB
Ghisleni
Gabriele
G
Tavares
Rejane G
RG
Souza
Diogo O
DO
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019793:Fluorescein; D005971:Glutamates / Q000378:metabolism*; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects; D014316:Tritium
D000975:Antioxidants; D001393:Azoles; D005971:Glutamates; D054833:Isoindoles; D016566:Organoselenium Compounds; D014316:Tritium; C042986:ebselen; D000254:Sodium-Potassium-Exchanging ATPase; D004229:Dithiothreitol; D019793:Fluorescein