NAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells

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dc.contributor.authorPereira, Gustavo José da Silva [UNIFESP]
dc.contributor.authorHirata, Hanako [UNIFESP]
dc.contributor.authorGarcez-do-Carmo, Lucia [UNIFESP]
dc.contributor.authorStilhano, Roberta Sessa [UNIFESP]
dc.contributor.authorUreshino, Rodrigo Portes [UNIFESP]
dc.contributor.authorMedaglia, Natalia de Castro [UNIFESP]
dc.contributor.authorHan, Sang Won [UNIFESP]
dc.contributor.authorChurchill, Grant
dc.contributor.authorBincoletto, Claudia [UNIFESP]
dc.contributor.authorPatel, Sandip
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Oxford
dc.contributor.institutionUCL
dc.date.accessioned2016-01-24T14:37:39Z
dc.date.available2016-01-24T14:37:39Z
dc.date.issued2014-08-01
dc.description.abstractNicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an important modulator of Ca2+ release from the endo-lysosomal system in a variety of cells by a new and ubiquitous class of endo-lysosomal ion channels known as the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth muscle is not known. in the present work, we investigated the effects of NAADP in gastric smooth muscle cells and its ability to release Ca2+ by TPCs. We show that Ca2+ signals mediated by NAADP were inhibited by disrupting Ca2+ handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous TPC1 and TPC2 were readily detected and recombinant TPCs localized to the endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants enhanced NAADP-mediated cytosolic Ca2+ signals. Desensitizing the NAADP pathway inhibited Ca2+-responses to extracellular stimulation with carbachol but not ATP. Taken together, these results indicate that NAADP likely induces Ca2+ release from the endolysosomal system through TPCs which is subsequently amplified via the ER in an agonist-specific manner. Thus, we suggest a second messenger role for NAADP in smooth muscle cells. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationFed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Oxford, Dept Pharmacol, Oxford OX1 3QT, England
dc.description.affiliationUCL, Dept Cell & Dev Biol, London, England
dc.description.affiliationUnifespFed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2016-01-24T14:37:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-01en
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council
dc.description.sponsorshipIDFAPESP: 2008/11.515-3pt
dc.description.sponsorshipIDCNPq: 482030/2010-0pt
dc.description.sponsorshipIDCAPES: BB/G013721/1pt
dc.format.extent51-58
dc.identifierhttps://dx.doi.org/10.1016/j.ceca.2014.04.005
dc.identifier.citationCell Calcium. Edinburgh: Churchill Livingstone, v. 56, n. 2, p. 51-58, 2014.
dc.identifier.doi10.1016/j.ceca.2014.04.005
dc.identifier.issn0143-4160
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/38044
dc.identifier.wosWOS:000340323600002
dc.language.isoeng
dc.publisherChurchill Livingstone
dc.relation.ispartofCell Calcium
dc.rightsAcesso restrito
dc.subjectNAADPen
dc.subjectTPCsen
dc.subjectCa2+en
dc.subjectLysosomesen
dc.subjectGastric smooth muscle cellsen
dc.titleNAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cellsen
dc.typeArtigo
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