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dc.contributor.author Cinalli, Alejandro Raúl
dc.contributor.author Guarracino, Juan Francisco
dc.contributor.author Fernández, Verónica Guillermina
dc.contributor.author Roquel, L. I.
dc.contributor.author Losavio, Adriana Silvia
dc.date.available 2017-07-13T20:54:39Z
dc.date.issued 2013-08
dc.identifier.citation Cinalli, Alejandro Raúl; Guarracino, Juan Francisco; Fernández, Verónica Guillermina; Roquel, L. I.; Losavio, Adriana Silvia; Inosine induces presynaptic inhibition of acetylcholine release by activation of A3 adenosine receptors at the mouse neuromuscular junction; Wiley; British Journal of Pharmacology; 169; 8; 8-2013; 1810-1823
dc.identifier.issn 0007-1188
dc.identifier.uri http://hdl.handle.net/11336/20426
dc.description.abstract BACKGROUND AND PURPOSE: The role of inosine at the mammalian neuromuscular junction (NMJ) has not been clearly defined. Moreover, inosine was classically considered to be the inactive metabolite of adenosine. Hence, we investigated the effect of inosine on spontaneous and evoked ACh release, the mechanism underlying its modulatory action and the receptor type and signal transduction pathway involved. EXPERIMENTAL APPROACH: End-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) were recorded from the mouse phrenic-nerve diaphragm preparations using conventional intracellular electrophysiological techniques. KEY RESULTS: Inosine (100 μM) reduced MEPP frequency and the amplitude and quantal content of EPPs; effects inhibited by the selective A3 receptor antagonist MRS-1191. Immunohistochemical assays confirmed the presence of A3 receptors at mammalian NMJ. The voltage-gated calcium channel (VGCC) blocker Cd(2+) , the removal of extracellular Ca(2+) and the L-type and P/Q-type VGCC antagonists, nitrendipine and ω-agatoxin IVA, respectively, all prevented inosine-induced inhibition. In the absence of endogenous adenosine, inosine decreased the hypertonic response. The effects of inosine on ACh release were prevented by the Gi/o protein inhibitor N-ethylmaleimide, PKC antagonist chelerytrine and calmodulin antagonist W-7, but not by PKA antagonists, H-89 and KT-5720, or the inhibitor of CaMKII KN-62. CONCLUSION AND IMPLICATIONS: Our results suggest that, at motor nerve terminals, inosine induces presynaptic inhibition of spontaneous and evoked ACh release by activating A3 receptors through a mechanism that involves L-type and P/Q-type VGCCs and the secretory machinery downstream of calcium influx. A3 receptors appear to be coupled to Gi/o protein. PKC and calmodulin may be involved in these effects of inosine.
dc.format application/pdf
dc.language.iso eng
dc.publisher Wiley
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject INOSINE
dc.subject A3 ADENOSINE RECEPTOR
dc.subject PRESYNAPTIC INHIBITION
dc.subject VOLTAGE-GATED CALCIUM CHANNELS
dc.subject Ca2+-INDEPENDENT MECHANISM
dc.subject MAMMALIAN NEUROMUSCULAR JUNCTION
dc.subject PCK
dc.subject.classification Biofísica
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Inosine induces presynaptic inhibition of acetylcholine release by activation of A3 adenosine receptors at the mouse neuromuscular junction
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-07-13T17:23:48Z
dc.identifier.eissn 1476-5381
dc.journal.volume 169
dc.journal.number 8
dc.journal.pagination 1810-1823
dc.journal.pais Estados Unidos
dc.journal.ciudad Hoboken
dc.description.fil Fil: Cinalli, Alejandro Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil Fil: Guarracino, Juan Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil Fil: Fernández, Verónica Guillermina. Universidad Argentina "John F. Kennedy"; Argentina
dc.description.fil Fil: Roquel, L. I.. Universidad Argentina "John F. Kennedy"; Argentina
dc.description.fil Fil: Losavio, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.journal.title British Journal of Pharmacology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/bph.12262/full
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/bph.12262
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753837/


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)