Amplification of neuromuscular transmission by methylprednisolone involves activation of presynaptic facilitatory adenosine A(2A) receptors and redistribution of synaptic vesicles

Página do item simplificado
dc.contributor.authorOliveira, L.
dc.contributor.authorCosta, A. C.
dc.contributor.authorNoronha-Matos, J. B.
dc.contributor.authorSilva, I.
dc.contributor.authorCavalcante, Walter Luís Garrido [UNESP]
dc.contributor.authorTimoteo, M. A.
dc.contributor.authorCorrado, A. P.
dc.contributor.authorDal Belo, C. A.
dc.contributor.authorAmbiel, C. R.
dc.contributor.authorAlves-do-Prado, W.
dc.contributor.authorCorreia-de-Sa, P.
dc.contributor.institutionUniv Porto
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do Pampa (UNIPAMPA)
dc.contributor.institutionUniversidade Estadual de Maringá (UEM)
dc.date.accessioned2015-10-21T13:11:08Z
dc.date.available2015-10-21T13:11:08Z
dc.date.issued2015-02-01
dc.description.abstractThe mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A(2A) receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [H-3]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A(2A) receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (03 mM)-induced transmitter release facilitation, because its effect was prevented by the A(2A) receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M-1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M-2 and Al receptors blocked by methoctramine (0.1 mu M) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A(2A) receptors by endogenous adenosine leading to synaptic vesicle redistribution. (C) 2014 Elsevier Ltd. All rights reserved.en
dc.description.affiliationUniv Porto, UMIB, Lab Farmacol &Neurobiol, P-4050313 Oporto, Portugal
dc.description.affiliationUniv Porto, Ctr Drug Discovery &Innovat Med MedInUP, P-4050313 Oporto, Portugal
dc.description.affiliationUNESP, Inst Biociencias, Botucatu, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Sao Gabriel, Rio Grande Do S, Brazil
dc.description.affiliationUniv Fed Pampa, Sao Gabriel, Rio Grande Do S, Brazil
dc.description.affiliationUniv Estadual Maringa, Dept Ciencias Fisiol, Maringa, Parana, Brazil
dc.description.affiliationUniv Estadual Maringa, Dept Farmacol &Terapeut, Maringa, Parana, Brazil
dc.description.affiliationUnespUNESP, Departamento de Física e Biofísica, Inst Biociencias, Botucatu, SP, Brazil
dc.description.sponsorshipFundação para a Ciência e a Tecnologia (FCT)
dc.description.sponsorshipFoundation of Research and Development of the State University of Maringa (FADEC-UEM)
dc.description.sponsorshipIdFCT: Pest/OE/U10215/2014
dc.description.sponsorshipIdFCT: SRFH/BD/68584/2010
dc.description.sponsorshipIdFCT: SFRH/BD/88855/2012
dc.format.extent64-76
dc.identifierhttp://www.sciencedirect.com/science/article/pii/S0028390814003116
dc.identifier.citationNeuropharmacology, v. 89, p. 64-76, 2015.
dc.identifier.doi10.1016/j.neuropharm.2014.09.004
dc.identifier.issn0028-3908
dc.identifier.urihttp://hdl.handle.net/11449/128576
dc.identifier.wosWOS:000347597600007
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofNeuropharmacology
dc.relation.ispartofjcr4.249
dc.relation.ispartofsjr2,043
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectNeuromuscular junctionen
dc.subjectSynaptic vesicle recyclingen
dc.subjectAcetylcholine releaseen
dc.subjectGlucocorticoidsen
dc.subjectAdenosine receptorsen
dc.subjectMuscarinic receptorsen
dc.titleAmplification of neuromuscular transmission by methylprednisolone involves activation of presynaptic facilitatory adenosine A(2A) receptors and redistribution of synaptic vesiclesen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

Arquivos

Coleções

Artigos - Física e Biofísica - IBB