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 occurring plant and fungal neurotoxin, exerts its neurotoxic effects are not fully understood. However, blockage of ATP synthesis by the irreversible inhibition of succinate dehydrogenase activity, increased production of free radicals, and secondary excitotoxicity have been implicated in its actions. In the present study, synaptic vesicle preparations from brain of adult rats 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 incorporation 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 uptake. Moreover, 3-NP did not inhibit the ATPase activity of synaptic vesicles. These findings indicate that low concentrations of 3-NP are able to selectively prevent vesicular glutamate storage, and this may represent at least one of the mechanisms responsible for the neurotoxic effects of 3-NP.
Tavares
R G
RG
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
Santos
C E
CE
Tasca
C I
CI
Wajner
M
M
Souza
D O
DO
Dutra-Filho
C S
CS
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D005998:Glycine / Q000493:pharmacokinetics; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics
D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000251:Adenosine Triphosphatases; C015392:3-nitropropionic acid; D005998:Glycine