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

Autor(es)

Pizzo, Andrea B. ^[1] ; Beleboni, Rene O. ^[2] ; Gomes Carolino, Ruither O. ^[3] ; de Oliveira, Luciana ^[1] ; Miranda, Antonio ^[4] ; Coutinho-Netto, Joaquim ^[3] ; Fontana, Andreia C. K. ^[5] ; dos Santos, Wagner Ferreira ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Coll Philosophy Sci & Literature FFCLRP, Lab Neurobiol & Venoms, FFCLRPAv, Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Ribeirao Preto UNAERP, Biotecnol Dept, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, Lab Neurochem, Ribeirao Preto - Brazil

^[4] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[5] Drexel Univ, Dept Physiol & Pharmacol, Coll Med, Philadelphia, PA 19104 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY; v. 31, n. 10 OCT 2017.
• Citações Web of Science: 0

Resumo

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. (AU)

• 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
• Processo FAPESP: 00/08010-5 - Caracterizacao quimica e atividade biologica de fracoes isoladas da peconha da vespa social agelaia vicina (hymenoptera vespidae).
• Beneficiário: Andrea Baldocchi Pizzo
• Modalidade de apoio: Bolsas no Brasil - Doutorado