Inhibition of glutamate uptake into synaptic vesicles from rat brain by 3-nitropropionic acid in vitro

The exact mechanisms by which 3-nitropropionic acid (3-NP), a naturally occ urring plant and fungal neurotoxin, exerts its neurotoxic effects are not f ully understood. However, blockage of ATP synthesis by the irreversible inh ibition of succinate dehydrogenase activity, increased production of free r adicals, and secondary excitotoxicity have been implicated in its actions. In the present study, synaptic vesicle preparations from brain of adult rat s were incubated with 3-NP at final concentrations ranging from 0.01 to 10 mM for the determination of glutamate uptake. The effect of 3-NP on gamma - aminobutyric acid (GABA) and glycine uptake was also studied. Glutamate inc orporation into vesicles was inhibited by 3-NP in a dose-dependent manner, whereas doses of up to 10 mM neurotoxin did not affect GABA or glycine upta ke. Moreover, 3-NP did not inhibit the ATPase activity of synaptic vesicles . These findings indicate that low concentrations of 3-NP are able to selec tively prevent vesicular glutamate storage, and this may represent at least one of the mechanisms responsible for the neurotoxic effects of 3-NP. (C) 2001 Academic Press.