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Type: Artigo de periódico
Title: Vdtx-1, A Reversible Nicotinic Receptor Antagonist Isolated From Venom Of The Spider Vitalius Dubius (theraphosidae).
Author: Rocha-E-Silva, Thomaz A A
Rostelato-Ferreira, Sandro
Leite, Gildo B
da Silva, Pedro Ismael
Hyslop, Stephen
Rodrigues-Simioni, Léa
Abstract: Theraphosid spider venoms can block neurotransmission in vertebrate nerve-muscle preparations in vitro, but few of the components involved have been characterized. In this work, we describe the neuromuscular activity of venom from the Brazilian theraphosid Vitalius dubius and report the purification and pharmacological characterization of VdTX-1, a 728 Da toxin that blocks nicotinic receptors. Neuromuscular activity was assayed in chick biventer cervicis preparations and muscle responses to exogenous ACh and KCl were determined before and after incubation with venom or toxin. Changes in membrane resting potential were studied in mouse diaphragm muscle. The toxin was purified by a combination of filtration through Amicon® filters, cation exchange HPLC and RP-HPLC; toxin purity and mass were confirmed by mass spectrometry. Venom caused progressive neuromuscular blockade and muscle contracture; the blockade but not the contracture was reversible by washing. Venom attenuated contractures to exogenous ACh and KCl. Filtration yielded low (LM, <5 kDa) and high (HM, >5 kDa) fractions, with the latter reproducing the contracture seen in venom but with a slight and progressive twitch blockade. The LM fraction caused reversible blockade and attenuated contractures to ACh, but had no effect on contractures to KCl. VdTX-1 (728 Da) purified from the LM fraction was photosensitive and reduced the E(max) to ACh in biventer cervicis muscle without affecting the EC₅₀; VdTX-1 also abolished carbachol-induced depolarizations. V. dubius venom contains at least two components that affect vertebrate neurotransmission. One component, VdTX-1, blocks nicotinic receptors non-competitively to produce reversible blockade without muscle contracture.
Subject: Animals
Chromatography, High Pressure Liquid
Neuromuscular Blockade
Neuromuscular Junction
Nicotinic Antagonists
Receptors, Nicotinic
Spectrometry, Mass, Matrix-assisted Laser Desorption-ionization
Spider Venoms
Synaptic Transmission
Citation: Toxicon : Official Journal Of The International Society On Toxinology. v. 70, p. 135-41, 2013-Aug.
Rights: fechado
Identifier DOI: 10.1016/j.toxicon.2013.04.020
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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