BAL modulates glutamate transport in synaptosomes and synaptic vesicles from rat brain.
The therapeutic use of BAL (2,3-dimercaptopropanol) as treatment for poisoning has been halted by data suggesting serious neurotoxicity. This article is a report on the effects of BAL and other dithiols, DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercaptopropane-1-sulfonic acid), on [3H]glutamate release and uptake by rat brain synaptosomes and [3H]glutamate uptake by synaptic vesicles. BAL (100 microM) inhibited glutamate uptake (30%) and stimulated its basal release (30%) in synaptosomes, without affecting K+-stimulated release. BAL also inhibited glutamate uptake by synaptic vesicles (up to 60%). DMPS and DMSA (100 microM) had no significant effects on these parameters. The data reported here provide some evidence of glutamate involvement in BAL-induced neurotoxicity by demonstrating direct effects of BAL on glutamatergic system modulation.
Nogueira
C W
CW
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Rotta
L L
LL
Tavares
R G
RG
Souza
D O
DO
Rocha
J B
JB
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002614:Chelating Agents / Q000633:toxicity*; D004112:Dimercaprol / Q000633:toxicity*; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000633:toxicity; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D014316:Tritium; D014494:Unithiol / Q000633:toxicity
D002614:Chelating Agents; D004112:Dimercaprol; D014316:Tritium; D018698:Glutamic Acid; D014494:Unithiol; D004113:Succimer; D011188:Potassium