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da Silva, Carolina Nunes
[1]
;
Lomeo, Rosangela Silva
[1]
;
Torres, Fernando Silva
[1]
;
Borges, Marcia Helena
[2]
;
Nascimento, Marta Cordeiro
[2]
;
Rodrigues Mesquita-Britto, Maria Helena
[3]
;
Raposo, Catarina
[3]
;
de Castro Pimenta, Adriano Monteiro
[1]
;
da Cruz-Hofling, Maria Alice
[3]
;
Gomes, Dawidson Assis
[1]
;
de Lima, Maria Elena
[1, 4]
Número total de Autores: 11
|
| Afiliação do(s) autor(es): | [1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG - Brazil
[2] Fundacao Ezequiel Dias FUNED, Ctr Pesquisa & Desenvolvimento, Belo Horizonte, MG - Brazil
[3] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, UNICAMP, Campinas, SP - Brazil
[4] Inst Ensino & Pesquisa Santa Casa Belo Horizonte, Grp Santa Casa Belo Horizonte, Programa Posgrad Ciencias Saude Biomed & Med, Belo Horizonte, MG - Brazil
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Toxicon; v. 150, p. 280-288, AUG 2018. |
| Citações Web of Science: | 1 |
| Resumo | |
PhTx2 is the most toxic fraction from the venom of the spider Phoneutria nigriventer, being responsible to sodium entry into cortical synaptosomes, increasing the release of neurotransmitters, such as L-glutamate (L-Glu) and; acetylcholine. In this study, we investigated the action of a toxin purified from; PhTx2 fraction, called PnTx2-6 or delta-CNTX-Pn2a, on L-Glu release from rat; brain cortex synaptosomes, as well as its ability to induce blood-brain barrier permeability. PnTx2-6 increased L-Glu release from rat cortical brain synaptosomes in a time- and dose dependent manner (EC50 = similar to 20 nM; Tm = 16min), as measured by a fluorimetric method. The increase of L-Glu by PnTx2-6 was inhibited by tetrodotoxin. And partially inhibited by EGTA. Calcium channel blockers omega-coconotoxin MVIIC (P/Q-types) and omega-conotoxin GVIA (N-type), were able to reduce the PnTx2-6-induced release of L-Glu, while nifedipine (L-type) did not show any inhibition. These findings suggest that thew release of L-Glu by PnTx2-6 is due its primary action on sodium channels, well-known to be target of this toxin. PnTx2-6 is able to potentiate penile erection and this effect may be related with the release of c-glutamate from the CNS, besides a local effect on corpus carvenosum, as previously shown by our group. If L-Glu release and penile erection potentiation are indeed correlated, then this toxin should be able to cross the blood brain barrier (BBB). Results by immunoblotting assays indicated a change in the expression of proteins associated with the paracellular and transcellular transport at the blood-brain barrier, suggesting a BBB dysfunction mediated by PnTx2-6. Therefore, PnTx2-6 may induce the release L-glutamate in the central nervous system, when injected peripherally. (AU) | |
| Processo FAPESP: | 15/04194-0 - Identificação de novas moléculas com efeito quimioterápico em glioma humano e caracterização do seu mecanismo de ação |
| Beneficiário: | Catarina Raposo Dias Carneiro |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |