Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: Radiochemical and real-time video-microscopy studies

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dc.contributor.authorCorreia-de-Sá, Paulo
dc.contributor.authorNoronha-Matos, José B.
dc.contributor.authorTimóteo, Maria A.
dc.contributor.authorFerreirinha, Fátima
dc.contributor.authorMarques, Patrícia
dc.contributor.authorSoares, Andreimar M.
dc.contributor.authorCarvalho, Cicilia [UNESP]
dc.contributor.authorCavalcante, Walter L.G. [UNESP]
dc.contributor.authorGallacci, Márcia [UNESP]
dc.contributor.institutionUniv. Porto
dc.contributor.institutionUNIR
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-27T11:27:29Z
dc.date.available2014-05-27T11:27:29Z
dc.date.issued2013-01-01
dc.description.abstractUnderstanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA2 homologue from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 μM) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [3H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. © 2012 Elsevier Ltd.en
dc.description.affiliationInstituto de Ciências Biomédicas de Abel Salazar UMIB Univ. Porto, 4099-003 Portoz
dc.description.affiliationUniversidade Federal de Rondônia UNIR
dc.description.affiliationInstituto de Biociências UNESP, Botucatu, 18618-970 São Paulo
dc.description.affiliationUnespInstituto de Biociências UNESP, Botucatu, 18618-970 São Paulo
dc.format.extent16-25
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2012.10.014
dc.identifier.citationToxicon, v. 61, n. 1, p. 16-25, 2013.
dc.identifier.doi10.1016/j.toxicon.2012.10.014
dc.identifier.issn0041-0101
dc.identifier.issn1879-3150
dc.identifier.lattes9353490382598257
dc.identifier.scopus2-s2.0-84870206270
dc.identifier.urihttp://hdl.handle.net/11449/74201
dc.identifier.wosWOS:000314146400003
dc.language.isoeng
dc.relation.ispartofToxicon
dc.relation.ispartofjcr2.352
dc.relation.ispartofsjr0,692
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subject[3H]-Acetylcholine release
dc.subjectBothropstoxin-I
dc.subjectNeuromuscular transmission
dc.subjectPhospholipase A2
dc.subjectReal-time transmitter exocytosis
dc.subjectSnake venom
dc.subjectBothropstoxin I
dc.subjectcalcium independent phospholipase A2
dc.subjectlactate dehydrogenase
dc.subjectsnake venom
dc.subjectunclassified drug
dc.subjectacetylcholine release
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectBothrops
dc.subjectbothrops jararacussu
dc.subjectcatalysis
dc.subjectcontrolled study
dc.subjectevoked response
dc.subjectexocytosis
dc.subjectfemale
dc.subjectfluorescence analysis
dc.subjecthistopathology
dc.subjectin vitro study
dc.subjectintracellular space
dc.subjectmale
dc.subjectmuscle necrosis
dc.subjectnerve cell membrane steady potential
dc.subjectnerve ending
dc.subjectneuromuscular blocking
dc.subjectnonhuman
dc.subjectpostsynaptic potential
dc.subjectpresynaptic potential
dc.subjectpriority journal
dc.subjectquantitative analysis
dc.subjectradioassay
dc.subjectrat
dc.subjectskeletal muscle
dc.subjecttoxin analysis
dc.subjectvideo microscopy
dc.subjectAcetylcholine
dc.subjectAnimals
dc.subjectCrotalid Venoms
dc.subjectDiaphragm
dc.subjectExocytosis
dc.subjectFemale
dc.subjectFluorescent Dyes
dc.subjectL-Lactate Dehydrogenase
dc.subjectMale
dc.subjectMicroelectrodes
dc.subjectMicroscopy, Video
dc.subjectMotor Neurons
dc.subjectMuscle Contraction
dc.subjectMyography
dc.subjectPhospholipases A2
dc.subjectPhrenic Nerve
dc.subjectPresynaptic Terminals
dc.subjectPyridinium Compounds
dc.subjectQuaternary Ammonium Compounds
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectBothrops jararacussu
dc.subjectRattus
dc.titleBothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: Radiochemical and real-time video-microscopy studiesen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
unesp.author.lattes9353490382598257
unesp.author.orcid0000-0001-6397-2104[2]
unesp.author.orcid0000-0002-6114-9189[1]
unesp.author.orcid0000-0002-4254-380X[3]
unesp.author.orcid0000-0002-0527-1323[4]
unesp.author.orcid0000-0001-6149-4030[9]
unesp.author.orcid0000-0002-2354-636X[8]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

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