PnTx2-6 (or delta-CNTX-Pn2a), a toxin from Phoneutria nigriventer spider venom, releases L-glutamate from rat brain synaptosomes involving Na+ and Ca2+ channels and changes protein expression at the blood-brain barrier

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Toxicon; v. 150, p. 280-288, AUG 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 15/04194-0 - Identification of new molecules with chemotherapeutic effect in human glioma and characterization of the mechanism
• Grantee: Catarina Raposo Dias Carneiro
• Support Opportunities: Research Grants - Young Investigators Grants