Quinolinic Acid-induced Seizures Stimulate Glutamate Uptake into Synaptic Vesicles from Rat Brain: Effects Prevented by Guanine-based Purines |
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Authors: | Rejane G Tavares André P Schmidt Carla I Tasca Diogo O Souza |
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Institution: | (1) Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Avenida Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil;(2) Department of Biochemistry, CCB, Federal University of Santa Catarina, Florianópolis, SC, Brazil |
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Abstract: | Glutamate uptake into synaptic vesicles is a vital step for glutamatergic neurotransmission. Quinolinic acid (QA) is an endogenous
glutamate analog that may be involved in the etiology of epilepsy and is related to disturbances on glutamate release and
uptake. Guanine-based purines (GBPs) guanosine 5′-monophosphate (GMP and guanosine) have been shown to exert anticonvulsant
effects against QA-induced seizures. The aims of this study were to investigate the effects of in vivo administration of several
convulsant agents on glutamate uptake into synaptic vesicles and investigate the role of MK-801, guanosine or GMP (anticonvulsants)
on glutamate uptake into synaptic vesicles from rats presenting QA-induced seizures. Animals were treated with vehicle (saline
0.9%), QA 239.2 nmoles, kainate 30 mg/kg, picrotoxin 6 mg/kg, PTZ (pentylenetetrazole) 60 mg/kg, caffeine 150 mg/kg or MES
(maximal transcorneal electroshock) 80 mA. All convulsant agents induced seizures in 80–100% of animals, but only QA stimulated
glutamate uptake into synaptic vesicle. Guanosine or GMP prevented seizures induced by QA (up to 52% of protection), an effect
similar to the NMDA antagonist MK-801 (60% of protection). Both GBPs and MK-801 prevented QA-induced glutamate uptake stimulation.
This study provided additional evidence on the role of QA and GBPs on glutamatergic system in rat brain, and point to new
perspectives on seizures treatment. |
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Keywords: | Guanosine GMP Quinolinic acid Glutamate uptake Epilepsy Synaptic vesicles |
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