Analgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibition

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dc.contributor.authorDale, Camila Squarzoni
dc.contributor.authorAltier, Christophe
dc.contributor.authorCenac, Nicolas
dc.contributor.authorGiorgi, Renata
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorZamponi, Gerald W.
dc.contributor.authorVergnolle, Nathalie
dc.contributor.institutionINSERM
dc.contributor.institutionUniv Toulouse 3
dc.contributor.institutionUniv Calgary
dc.contributor.institutionButantan Inst
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:58:37Z
dc.date.available2016-01-24T13:58:37Z
dc.date.issued2009-08-01
dc.description.abstractCalcium-binding protein S100A9 and its C-terminus peptide (mS100A9p) are anti-inflammatory and induce antinociception in rodents. We investigated the mechanisms involved in this effect, and whether they depend or not on the anti-inflammatory properties of mS100A9p. in mice, mS100A9p inhibited thermal and mechanical hyperalgesia and allodynia induced by either carrageenan or formalin, without interfering with paw edema. mS100A9p also inhibited myeloperoxidase activity (MPO), a marker of granulocyte infiltration, induced by carrageenan, but increased MPO after formalin intraplantar injection. the in vivo analgesic properties of mS100A9p were independent of opioid receptor activation. Calcium flux into dorsal root ganglia neurons induced by KCl was inhibited by mS100A9p, suggesting that this protein is able to inhibit signaling, in sensory neurons. the inhibitory effects of mS100A9p on primary afferent signaling were neither due to intracellular calcium store inhibition nor to calcium chelating properties. However, mS100A9p was able to inhibit calcium currents carried by transiently expressed N-type, but not L-type calcium channels, as demonstrated both by gene transfection techniques and electrophysiology. These data demonstrate that mS100A9p interferes with mechanisms involved in nociception, hyperalgesia and calcium signaling in sensory neurons, modulating primary afferent nociceptive signal by inhibiting activation of N-type voltage operated calcium channels.en
dc.description.affiliationINSERM, U563, Ctr Physiopathol Toulouse Purpan, F-31300 Toulouse, France
dc.description.affiliationUniv Toulouse 3, F-31000 Toulouse, France
dc.description.affiliationUniv Calgary, Dept Physiol & Biophys, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada
dc.description.affiliationButantan Inst, Lab Pathophysiol, BR-05505900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, Inst Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Calgary, Dept Pharmacol & Therapeut, Calgary, AB T2N 4N1, Canada
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, Inst Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent427-438
dc.identifierhttp://dx.doi.org/10.1111/j.1472-8206.2009.00686.x
dc.identifier.citationFundamental & Clinical Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 23, n. 4, p. 427-438, 2009.
dc.identifier.doi10.1111/j.1472-8206.2009.00686.x
dc.identifier.issn0767-3981
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31735
dc.identifier.wosWOS:000268588700006
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofFundamental & Clinical Pharmacology
dc.rightsAcesso restrito
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectantinociceptionen
dc.subjectdorsal root ganglia neuronsen
dc.subjectinflammationen
dc.subjectN-type calcium channelsen
dc.subjectS100A9en
dc.subjectvoltage operated calcium channelsen
dc.titleAnalgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibitionen
dc.typeArtigo
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