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Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+Mobilization and Cell Proliferation

2013Journal article Open access
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dc.contributor.authorPinheiro, Ana Rita
dc.contributor.authorParamos-de-Carvalho, Diogo
dc.contributor.authorCertal, Mariana
dc.contributor.authorCosta, Maria Adelina
dc.contributor.authorCosta, Cristina
dc.contributor.authorMagalhães-Cardoso, Maria Teresa
dc.contributor.authorFerreirinha, Fátima
dc.contributor.authorSévigny, Jean
dc.contributor.authorCorreia-de-Sá, Paulo
dc.date.accessioned2019-07-11T13:31:50Z
dc.date.available2019-07-11T13:31:50Z
dc.date.issued2013
dc.description.abstractChanges in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca(2+) ([Ca(2+)]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca(2+)]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca(2+)]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with (10)Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca(2+)]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1074/jbc.M113.460865pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/14340
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationFIBROBLASTOS COMO INTERMEDIÁRIOS NA SINALIZAÇÃO MECANO-SENSITIVA ENTRE O EPITÉLIO E OS NEURÓNIOS AFE-RENTES PRIMÁRIOS: PAPEL DO ATP EXTRACELULAR E DAS ONDAS DE CA2+I
dc.relation.publisherversionhttp://www.jbc.org/content/288/38/27571.longpt_PT
dc.subjectAdenosine Diphosphatept_PT
dc.subjectAdenosine Triphosphatept_PT
dc.subjectAnti-Bacterial Agentspt_PT
dc.subjectAntimalarialspt_PT
dc.subjectBrefeldin Apt_PT
dc.subjectCalciumpt_PT
dc.subjectCell Proliferationpt_PT
dc.subjectCells, Culturedpt_PT
dc.subjectCollagen Type Ipt_PT
dc.subjectConnexinspt_PT
dc.subjectExocytosispt_PT
dc.subjectFibroblastspt_PT
dc.subjectGene Expression Regulationpt_PT
dc.subjectHistaminept_PT
dc.subjectHistamine Agonistspt_PT
dc.subjectMast Cellspt_PT
dc.subjectMefloquinept_PT
dc.subjectNerve Tissue Proteinspt_PT
dc.subjectOctanolspt_PT
dc.subjectPurinergic P2Y Receptor Antagonistspt_PT
dc.subjectReceptors, Histamine H1pt_PT
dc.subjectReceptors, Purinergic P2Y1pt_PT
dc.titleHistamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+Mobilization and Cell Proliferationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleFIBROBLASTOS COMO INTERMEDIÁRIOS NA SINALIZAÇÃO MECANO-SENSITIVA ENTRE O EPITÉLIO E OS NEURÓNIOS AFE-RENTES PRIMÁRIOS: PAPEL DO ATP EXTRACELULAR E DAS ONDAS DE CA2+I
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F47373%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-FCF%2F108263%2F2008/PT
oaire.citation.endPage27583pt_PT
oaire.citation.issue38pt_PT
oaire.citation.startPage27571pt_PT
oaire.citation.titleJournal of Biological Chemistrypt_PT
oaire.citation.volume288pt_PT
oaire.fundingStream5876-PPCDTI
person.familyNamePinheiro
person.givenNameAna Rita
person.identifier.orcid0000-0003-4310-7652
person.identifier.ridB-4018-2017
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationa99bce31-2fe7-4e36-af87-32d684d22ce0
relation.isAuthorOfPublication.latestForDiscoverya99bce31-2fe7-4e36-af87-32d684d22ce0
relation.isProjectOfPublicationd0691ec6-ec11-42b1-9672-e3cf0b6331d2
relation.isProjectOfPublication77917fd8-d964-4978-9354-1e6f217de19d
relation.isProjectOfPublication.latestForDiscovery77917fd8-d964-4978-9354-1e6f217de19d

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