Large-conductance channel formation mediated by P2X7 receptor activation is regulated through distinct intracellular signaling pathways in peritoneal macrophages and 2BH4 cells

dc.creatorFaria, R. X.
dc.creatorCascabulho, C. M.
dc.creatorReis, R. A. M.
dc.creatorAlves, Luiz Anastácio
dc.date2017-09-19T17:33:52Z
dc.date2017-09-19T17:33:52Z
dc.date2010
dc.date.accessioned2023-09-27T00:15:44Z
dc.date.available2023-09-27T00:15:44Z
dc.identifierFARIA, R. X. et al. Large-conductance channel formation mediated by P2X7 receptor activation is regulated through distinct intracellular signaling pathways in peritoneal macrophages and 2BH4 cells. Naunyn-Schmied Arch Pharmacol, v. 382, p.73–87, 2010.
dc.identifier0028-1298
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/21068
dc.identifier10.1007/s00210-010-0523-8
dc.identifier1432-1912
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8899074
dc.descriptionThe P2X(7) receptor (P2X7R) is a ligand-gated ATP receptor that acts as a low- and large-conductance channel (pore) and is known to be coupled to several downstream effectors. Recently, we demonstrated that the formation of a large-conductance channel associated with the P2X(7) receptor is induced by increasing the intracellular Ca(2+) concentration (Faria et al., Am J Physiol Cell Physiol 297:C28-C42, 2005). Here, we investigated the intracellular signaling pathways associated with P2X(7) large-conductance channel formation using the patch clamp technique in conjunction with fluorescent imaging and flow cytometry assays in 2BH4 cells and peritoneal macrophages. Different antagonists were applied to investigate the following pathways: Ca(2+)-calmodulin, phospholipase A, phospholipase D, phospholipase C, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), MAPK/extracellular signal-regulated kinase, phosphoinositide 3-kinase (PI3K), and cytoskeletal proteins. Macroscopic ionic currents induced by 1 mM ATP were reduced by 85% in the presence of PKC antagonists. The addition of antagonists for MAPK, PI3K, and the cytoskeleton (actin, intermediary filament, and microtubule) blocked 92%, 83%, and 95% of the ionic currents induced by 1 mM ATP, respectively. Our results show that PKC, MAPK, PI3K, and cytoskeletal components are involved in P2X(7) receptor large-channel formation in 2BH4 cells and peritoneal macrophages.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherSpringer Verlag (Germany)
dc.rightsrestricted access
dc.subjectReceptores Purinérgicos P2X7
dc.subjectmacrófagos peritoneais
dc.subjectSistemas do Segundo Mensageiro
dc.subjectformação de poros
dc.subjectP2X7 receptor
dc.subjectIntracellular Ca2+
dc.subjectPore formation
dc.subjectSecond messenger
dc.subjectperitoneal macrophages
dc.titleLarge-conductance channel formation mediated by P2X7 receptor activation is regulated through distinct intracellular signaling pathways in peritoneal macrophages and 2BH4 cells
dc.typeArticle


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