Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action.
Marques-da-Silva C, Chaves MM, Castro NG, Coutinho-Silva R, Guimaraes MZ.
???displayArticle.abstract???
The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton might affect the functions of these receptors.Functions of heterologously expressed P2X2 and P2X7 receptors were evaluated with electrophysiology and dye uptake following ATP application. Permeabilization and secretion of pro-inflammatory agents were quantified from fresh or cultured peritoneal mouse macrophages, treated in vitro or in vivo with colchicine.Disrupting the microtubule network with colchicine did not affect currents generated by ATP in P2X2 and P2X7 receptor-expressing cells but inhibited uptake of the dye Yo-Pro-1 in Xenopus oocytes and HEK293 cells expressing these channels. Peritoneal mouse macrophages showed less ATP-induced permeabilization to ethidium bromide in the presence of colchicine, and less reactive oxygen species (ROS) formation, nitric oxide (NO) and interleukin (IL)-1β release. Colchicine treatment did not affect ATP-evoked currents in macrophages. Finally, in vivo assays with mice inoculated with lipopolysaccharide and ATP showed diminished ROS, IL-1β, interferon-γ and NO production after colchicine treatment.Colchicine has known anti-inflammatory actions and is used to treat several conditions involving innate immunity, including gout and familial Mediterranean fever. Here we propose a new mechanism of action - inhibition of pore formation induced by activation of P2X receptors - which could explain some of the anti-inflammatory effects of colchicine.
Bezalel,
The 3435T polymorphism in the ABCB1 gene and colchicine unresponsiveness in familial Mediterranean fever.
2009, Pubmed
Bezalel,
The 3435T polymorphism in the ABCB1 gene and colchicine unresponsiveness in familial Mediterranean fever.
2009,
Pubmed Brône,
P2X currents in peritoneal macrophages of wild type and P2X4 -/- mice.
2007,
Pubmed Brough,
Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death.
2007,
Pubmed Castro,
Direct inhibition of the N-methyl-D-aspartate receptor channel by dopamine and (+)-SKF38393.
1999,
Pubmed Chia,
Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine.
2008,
Pubmed Coutinho-Silva,
P2Z purinoceptor-associated pores induced by extracellular ATP in macrophages and J774 cells.
1997,
Pubmed Cruz,
ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages.
2007,
Pubmed da Cruz,
Activation of ERK1/2 by extracellular nucleotides in macrophages is mediated by multiple P2 receptors independently of P2X7-associated pore or channel formation.
2006,
Pubmed Declèves,
Is P-glycoprotein (ABCB1) a phase 0 or a phase 3 colchicine transporter depending on colchicine exposure conditions?
2006,
Pubmed Denlinger,
Regulation of inducible nitric oxide synthase expression by macrophage purinoreceptors and calcium.
1996,
Pubmed de Oliveira-Pierce,
Colchicine: a novel positive allosteric modulator of the human 5-hydroxytryptamine3A receptor.
2009,
Pubmed
,
Xenbase Egan,
Biophysics of P2X receptors.
2006,
Pubmed Faria,
Large-conductance channel formation mediated by P2X7 receptor activation is regulated through distinct intracellular signaling pathways in peritoneal macrophages and 2BH4 cells.
2010,
Pubmed Ferrari,
The P2X7 receptor: a key player in IL-1 processing and release.
2006,
Pubmed Gaudry,
Crystal-induced neutrophil activation. III. Inflammatory microcrystals induce a distinct pattern of tyrosine phosphorylation in human neutrophils.
1993,
Pubmed Gendreau,
Identification of a tubulin binding motif on the P2X2 receptor.
2003,
Pubmed Gourine,
P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats.
2005,
Pubmed Gourine,
Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats.
2002,
Pubmed Gu,
Extracellular ATP dissociates nonmuscle myosin from P2X(7) complex: this dissociation regulates P2X(7) pore formation.
2009,
Pubmed Guimaraes,
Isoform specificity of P2X2 purinergic receptor C-terminus binding to tubulin.
2008,
Pubmed Hewinson,
A key role for redox signaling in rapid P2X7 receptor-induced IL-1 beta processing in human monocytes.
2008,
Pubmed Khakh,
Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds.
1999,
Pubmed Kim,
Proteomic and functional evidence for a P2X7 receptor signalling complex.
2001,
Pubmed Labasi,
Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response.
2002,
Pubmed Lammas,
ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors.
1997,
Pubmed Li,
Suppression of LPS-induced tumor necrosis factor-alpha gene expression by microtubule disrupting agents.
1996,
Pubmed Martinon,
Gout-associated uric acid crystals activate the NALP3 inflammasome.
2006,
Pubmed Martinon,
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
2002,
Pubmed Müller-Peddinghaus,
The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers.
1987,
Pubmed North,
Molecular physiology of P2X receptors.
2002,
Pubmed Nuki,
Colchicine: its mechanism of action and efficacy in crystal-induced inflammation.
2008,
Pubmed NULL,
Guide to Receptors and Channels (GRAC), 4th Edition.
2009,
Pubmed Parker,
Modulation of ATP-gated non-selective cation channel (P2X1 receptor) activation and desensitization by the actin cytoskeleton.
1998,
Pubmed Pelegrin,
P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage.
2008,
Pubmed Pelegrin,
Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.
2006,
Pubmed Pelegrin,
The P2X(7) receptor-pannexin connection to dye uptake and IL-1beta release.
2009,
Pubmed Pétrilli,
The inflammasome: a danger sensing complex triggering innate immunity.
2007,
Pubmed Pfeiffer,
The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho.
2004,
Pubmed Pfeiffer,
Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation.
2007,
Pubmed Piccini,
ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way.
2008,
Pubmed Raices,
A synergistic role for IL-1beta and TNFalpha in monocyte-derived IFNgamma inducing activity.
2008,
Pubmed Schachter,
ATP-induced P2X7-associated uptake of large molecules involves distinct mechanisms for cations and anions in macrophages.
2008,
Pubmed Schroder,
The inflammasomes.
2010,
Pubmed Silverman,
Probenecid, a gout remedy, inhibits pannexin 1 channels.
2008,
Pubmed
,
Xenbase Sim,
P2X1 and P2X4 receptor currents in mouse macrophages.
2007,
Pubmed Solle,
Altered cytokine production in mice lacking P2X(7) receptors.
2001,
Pubmed Sperlágh,
ATP released by LPS increases nitric oxide production in raw 264.7 macrophage cell line via P2Z/P2X7 receptors.
1998,
Pubmed Sundy,
Progress in the pharmacotherapy of gout.
2010,
Pubmed Takenouchi,
Modulation of the ATP-lnduced release and processing of IL-1beta in microglial cells.
2009,
Pubmed Takenouchi,
Lysophospholipids and ATP mutually suppress maturation and release of IL-1 beta in mouse microglial cells using a Rho-dependent pathway.
2008,
Pubmed Terkeltaub,
Colchicine update: 2008.
2009,
Pubmed Tonetti,
Extracellular ATP enhances mRNA levels of nitric oxide synthase and TNF-alpha in lipopolysaccharide-treated RAW 264.7 murine macrophages.
1995,
Pubmed Virginio,
Pore dilation of neuronal P2X receptor channels.
1999,
Pubmed Wallace,
Plasma levels of colchicine after oral administration of a single dose.
1973,
Pubmed Weiner,
Colchicine is a competitive antagonist at human recombinant gamma-aminobutyric acidA receptors.
1998,
Pubmed Zhang,
Macrophage activation by endogenous danger signals.
2008,
Pubmed
