Isolation and chemical characterization of agelaiatoxin8 (AvTx8) from Agelaia vicina wasp venom and its biological effects on GABA neurotransmission |
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Authors: | Andrea B Pizzo Renê O Beleboni Ruither O Gomes Carolino Luciana de Oliveira Antonio Miranda Andréia C K Fontana Wagner Ferreira dos Santos |
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Institution: | 1. Laboratory of Neurobiology and Venoms, College of Philosophy, Sciences and Literature (FFCLRP), University of S?o Paulo, Ribeir?o Preto, Brazil;2. Biotecnology Department, Universidade de Ribeir?o Preto (UNAERP), Ribeir?o Preto, Brazil;3. Laboratory of Neurochemistry, Department of Biochemistry and Immunology,Ribeirao Preto School of Medicine, University of S?o Paulo, Ribeir?o Preto, Brazil;4. Department of Biophysics, Federal University of S?o Paulo, S?o Paulo, Brazil;5. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA |
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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 γ‐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 1567 Da. 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. |
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Keywords: | Agelaia vicina AvTx8 GABA neurotransmission wasp venom |
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