Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake

Autor(es)

Fontana, A. C. K. ; Guizzo, R. ; Beleboni, R. de O. ; Meirelles e Silva, A. R. ; Amara, S. G. ; Santos, W. F. dos ; Coutinho-Netto, J. ; Coimbra, N. C. ^[8]

• Tipo de documento: Artigo Científico
• Fonte: British Journal of Pharmacology; v. 139, n. 7, p. 1297-1309, Aug. 2003.
• Área do conhecimento: Ciências Biológicas - Farmacologia
• Assunto(s): Venenos de origem animal Sistema nervoso central

Resumo

In this study, we examined the effects of crude venom from the spider Parawixia bistriata on glutamate and GABA uptake into synaptosomes prepared from rat cerebral cortex. Addition of venom to cortical synaptosomes stimulated glutamate uptake and inhibited GABA uptake in a concentration-dependent manner. The venom was fractionated using reverse-phase high-performance liquid chromatography on a preparative column. The fraction that retained glutamate uptake-stimulating activity was further purified on a reverse-phase analytical column followed by ion-exchange chromatography. The active fraction, referred to as PbTx1.2.3, stimulated glutamate uptake in synaptosomes without changing the KM value, and did not affect GABA uptake. Additional experiments showed that the enhancement of glutamate uptake by PbTx1.2.3 occurs when ionotropic glutamate receptors or voltage-gated sodium and calcium channels are completely inhibited or when GABA receptors and potassium channels are activated, indicating that the compound may have a direct action on the transporters. In an experimental model for glaucoma in which rat retinas are subjected to ischemia followed by reperfusion, PbTx1.2.3 protected neurons from excitotoxic death in both outer and inner nuclear layers, and ganglion cell layers. (AU)

• Processo FAPESP: 99/01346-9 - Efeito dos antagonistas de receptores excitatórios, nimodipina e lamotrigina, e alguns componentes da peçonha da aranha Parawixia bistriata na lesão neuronial seletiva por isquemia seguida de reperfusão: análise histológica
• Beneficiário: Renato Guizzo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 00/08101-0 - Caracterizacao bioquimica e mecanismo de acao de fracoes cromatograficas purificadas da peconha da aranha social (parawixia bistriata).
• Beneficiário: Renê de Oliveira Beleboni
• Modalidade de apoio: Bolsas no Brasil - Doutorado