title: Purinergic receptors: new targets for the treatment of gout and fibrosis.
abstract: Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, adenosine 5'-triphosphate (ATP) can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells. P2X7R is known to regulate the activation of the Nod-like receptor (NLR)-family protein, NLRP3 inflammasome, which permit the release of IL-1β, a potent pro-inflammatory cytokine. The P2X7R/NLRP3 pathway is involved in many inflammatory diseases, such as gout, and in fibrosis diseases associated with inflammatory process, liver or lung fibrosis. Some authors imaging also a real promising therapeutic potential of P2X7R blockage. Thus, several pharmaceutical companies have developed P2X7R antagonists as novel anti-inflammatory drug candidates. Clinical trials of the efficacy of these antagonists are now underway. A better understanding of the P2X7R/NLRP3 signalling pathways permits the identification of targets and the development of a new class of drugs able to inhibit the fibrogenesis process and collagen deposition.
authors.affiliation: Laboratoire de toxicologie biologique et médico-légale, CHU Rennes, F-35033, Rennes, France.|UMR991 INSERM, Faculté de Pharmacie, Université Rennes 1, F-35043, Rennes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gicquel
authors.affiliation: UMR991 INSERM, Faculté de Pharmacie, Université Rennes 1, F-35043, Rennes, France.|CHU Rennes, Pôle Pharmacie, F-35033, Rennes, France.
authors.forename: Brendan
authors.initials: B
authors.lastname: Le Daré
authors.affiliation: UMR991 INSERM, Faculté de Pharmacie, Université Rennes 1, F-35043, Rennes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Boichot
authors.affiliation: UMR991 INSERM, Faculté de Pharmacie, Université Rennes 1, F-35043, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lagente
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015195:Drug Design; D005355:Fibrosis / Q000188:drug therapy* / Q000473:pathology; D006073:Gout / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000187:drug effects / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058920:Purinergic P2X Receptor Antagonists; D011983:Receptors, Purinergic; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: NLRP3-inflammasome; P2X7; adenosine 5′-triphosphate; fibrosis; inflammation; purinergic receptors