title: The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease.
abstract: The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but not exclusively, on immune cells. P2X7 activation results in a number of downstream events, including the release of proinflammatory mediators and cell death and proliferation. As such, P2X7 plays important roles in various inflammatory, immune, neurologic and musculoskeletal disorders. This review focuses on the use of P2X7 antagonists in rodent models of neurologic disease and injury, inflammation, and musculoskeletal and other disorders. The cloning and characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7, as well as recent observations regarding the gating and permeability of P2X7, are discussed. Furthermore, this review discusses polymorphic and splice variants of P2X7, as well as the generation and use of P2X7 knockout mice. Recent evidence for emerging signaling pathways downstream of P2X7 activation and the growing list of negative and positive modulators of P2X7 activation and expression are also described. In addition, the use of P2X7 antagonists in numerous rodent models of disease is extensively summarized. Finally, the use of P2X7 antagonists in clinical trials in humans and future directions exploring P2X7 as a therapeutic target are described.
authors.affiliation: School of Biological Sciences, University of Wollongong, New South Wales, Australia and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia (R.B., R.S.); and Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia (L.S.).
authors.forename: Rachael
authors.initials: R
authors.lastname: Bartlett
authors.affiliation: School of Biological Sciences, University of Wollongong, New South Wales, Australia and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia (R.B., R.S.); and Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia (L.S.).
authors.forename: Leanne
authors.initials: L
authors.lastname: Stokes
authors.affiliation: School of Biological Sciences, University of Wollongong, New South Wales, Australia and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia (R.B., R.S.); and Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia (L.S.) rsluyter@uow.edu.au.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sluyter
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D011110:Polymorphism, Genetic; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology*; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7