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.
Footnotes
This work was supported by an Australian Postgraduate Award from the University of Wollongong (to R.B.); the University of Wollongong Global Challenges Program (to R.B.); the National Health and Medical Research Council (to L.S.), an RMIT University Vice Chancellor’s Research Fellowship (to L.S.); the American Kennel Club Canine Health Foundation (to R.S. and L.S.); the University Research Committee of the University of Wollongong (to R.S.); and the Centre for Medical and Molecular Bioscience (to R.S.).
The authors declare no conflict of interest.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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In this issue
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- Article
- Abstract
- I. The P2X7 Receptor
- II. The Rodent P2X7 Receptor
- III. The Human P2X7 Receptor
- IV. P2X7 Receptors of Other Mammalian Species
- V. Gating of the P2X7 Receptor Channel
- VI. Permeability of the P2X7 Receptor
- VII. P2X7 Receptor-Dependent Signaling Pathways
- VIII. Variants of the P2X7 Receptor
- IX. Modulators of P2X7 Receptor Activation
- X. Use of Modulators of P2X7 Receptor In Vivo
- XI. P2X7 Antagonists in Human Clinical Trials
- XII. Modulators of P2X7 Receptor Expression
- XIII. Conclusions and Future Directions
- Acknowledgments
- Authorship Contributions
- Footnotes
- Abbreviations
- References
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