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

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dc.contributor.author Pereira, Gustavo J. S. [UNIFESP]
dc.contributor.author Hirata, Hanako [UNIFESP]
dc.contributor.author Garcez-do-Carmo, Lucia [UNIFESP]
dc.contributor.author Stilhano, Roberta S. [UNIFESP]
dc.contributor.author Ureshino, Rodrigo P. [UNIFESP]
dc.contributor.author Medaglia, Natalia C. [UNIFESP]
dc.contributor.author Han, Sang W. [UNIFESP]
dc.contributor.author Churchill, Grant
dc.contributor.author Bincoletto, Claudia [UNIFESP]
dc.contributor.author Patel, Sandip
dc.contributor.author Smaili, Soraya Soubhi [UNIFESP]
dc.date.accessioned 2016-01-24T14:37:39Z
dc.date.available 2016-01-24T14:37:39Z
dc.date.issued 2014-08-01
dc.identifier http://dx.doi.org/10.1016/j.ceca.2014.04.005
dc.identifier.citation Cell Calcium. Edinburgh: Churchill Livingstone, v. 56, n. 2, p. 51-58, 2014.
dc.identifier.issn 0143-4160
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/38044
dc.description.abstract Nicotinic 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.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Biotechnology and Biological Sciences Research Council
dc.format.extent 51-58
dc.language.iso eng
dc.publisher Churchill Livingstone
dc.relation.ispartof Cell Calcium
dc.rights Acesso restrito
dc.subject NAADP en
dc.subject TPCs en
dc.subject Ca2+ en
dc.subject Lysosomes en
dc.subject Gastric smooth muscle cells en
dc.title NAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Oxford
dc.contributor.institution UCL
dc.description.affiliation Fed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, Brazil
dc.description.affiliation Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
dc.description.affiliation UCL, Dept Cell & Dev Biol, London, England
dc.description.affiliationUnifesp Fed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2008/11.515-3
dc.description.sponsorshipID CNPq: 482030/2010-0
dc.description.sponsorshipID CAPES: BB/G013721/1
dc.identifier.doi 10.1016/j.ceca.2014.04.005
dc.description.source Web of Science
dc.identifier.wos WOS:000340323600002



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