In vivo quinolinic acid increases synaptosomal glutamate release in rats: reversal by guanosine.
Glutamate, the main excitatory neurotransmitter in the mammalian central nervous system (CNS), plays important role in brain physiological and pathological events. Quinolinic acid (QA) is a glutamatergic agent that induces seizures and is involved in the etiology of epilepsy. Guanine-based purines (GBPs) (guanosine and GMP) have been shown to exert neuroprotective effects against glutamatergic excitotoxic events. In this study, the influence of QA and GBPs on synaptosomal glutamate release and uptake in rats was investigated. We had previously demonstrated that QA "in vitro" stimulates synaptosomal L-[3H]glutamate release. In this work, we show that i.c.v. QA administration induced seizures in rats and was able to stimulate synaptosomal L-[3H]glutamate release. This in vivo neurochemical effect was prevented by i.p. guanosine only when this nucleoside prevented QA-induced seizures. I.c.v. QA did not affect synaptosomal L-[3H]glutamate uptake. These data provided new evidence on the role of QA and GBPs on glutamatergic system in rat brain.
Tavares
Rejane G
RG
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Schmidt
André P
AP
Abud
Jamile
J
Tasca
Carla I
CI
Souza
Diogo O
DO
D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D006151:Guanosine; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D017378:Quinolinic Acid