Isolation and chemical characterization of agelaiatoxin8 (AvTx8) from Agelaia vicina wasp venom and its biological effects on GABA neurotransmission

Isolation and chemical characterization of agelaiatoxin8 (AvTx8) from Agelaia vicina wasp venom and its biological effects on GABA neurotransmission

Author Pizzo, Andrea B. Google Scholar
Beleboni, Rene O. Google Scholar
Gomes Carolino, Ruither O. Google Scholar
de Oliveira, Luciana Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Coutinho-Netto, Joaquim Google Scholar
Fontana, Andreia C. K. Google Scholar
dos Santos, Wagner Ferreira Google Scholar
Abstract Arthropod venoms are sources of molecules that may be useful tools to investigate molecular mechanisms of putative new medicines and laboratory drugs. Here we show the effects of the compound agelaiatoxin-8 (AVTx8), isolated from Agelaia vicina venom, on -aminobutyric acid (GABA) neurotransmission in rat brain synaptosomes. Analysis reveals that AvTx8 is composed by 14 amino acid residues with a molecular weight (MW) of 1567Da. AvTx8 increased GABA release and inhibited GABA uptake in synaptosomes from rat cerebral cortex. AvTx8 inhibited GABA uptake and increased GABA release in the presence of Ca+, Na+, and K+ channel blockers, suggesting that it acts directly on GABA transporters. In addition, AvTx8 significantly decreases GABA binding in synaptic membranes from rat brain cortex, suggesting that it also modulates the activity of GABA receptors. Moreover, AvTx8 decreased GAT-1- and GAT-3-mediated GABA uptake in transfected COS-7 cells. Accordingly, we suggest that AvTx8 modulates GABA neurotransmission and might provide a novel entry point for identifying a new class of GABA-modulating neuroprotective drugs.
Keywords Agelaia vicina
AvTx8
GABA neurotransmission
wasp venom
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [FAPESP 00/08010-5, 00/08101-0]
Grant number FAPESP: 00/08010-5
FAPESP: 00/08101-0
Date 2017
Published in Journal Of Biochemical And Molecular Toxicology. Hoboken, v. 31, n. 10, p. -, 2017.
ISSN 1095-6670 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent -
Origin http://dx.doi.org/10.1002/jbt.21941
Access rights Closed access
Type Article
Web of Science ID WOS:000412328200001
URI https://repositorio.unifesp.br/handle/11600/57291

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