P2X4: A fast and sensitive purinergic receptor.
Jaanus Suurväli1, Pierre Boudinot2, Jean Kanellopoulos3
1Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Biomedical Journal
|November 29, 2017
Summary
The P2X4 receptor, a sensitive purinergic receptor, plays a key role in neuropathic pain and inflammation. Its gender-dependent expression and involvement in various pathologies highlight its potential as a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Extracellular nucleotides mediate responses via P2 receptors, including P2X ionotropic and P2Y G protein-coupled receptors.
- P2X receptors are implicated in diverse functions such as synaptic transmission, pain, inflammation, and cell activation.
- P2X4 is a highly sensitive purinergic receptor, significantly more so than P2X7, with broad expression in neurons, microglia, and endothelial cells.
Purpose of the Study:
- To elucidate the role and characteristics of the P2X4 receptor in physiological and pathological processes.
- To investigate the localization and activation mechanism of P2X4, particularly within intracellular compartments.
- To explore the involvement of P2X4 in pain, inflammation, and other diseases, and its potential as a therapeutic target.
Main Methods:
- Analysis of P2X4 receptor expression and localization in various cell types and tissues.
- Investigation of P2X4 activation kinetics and dependence on ATP concentration and pH.
- Examination of P2X4's role in pain pathways, inflammatory responses, and disease models.
Main Results:
- P2X4 is widely expressed and preferentially localized in lysosomes, where it is protected from proteolysis.
- Activation of P2X4 as a Ca2+ channel occurs after endosome-lysosome fusion, dependent on intra-lysosomal ATP and pH.
- P2X4 modulates neurotransmitter systems, alcohol responses, and is a key mediator of neuropathic pain, with injury-induced upregulation showing gender dependency.
- P2X4 contributes to inflammation, particularly in response to high extracellular ATP, and is implicated in pathologies like rheumatoid arthritis, asthma, and neurodegenerative diseases.
Conclusions:
- P2X4 receptor function is intricately linked to intracellular trafficking and activation mechanisms.
- The P2X4 receptor is a critical player in neuropathic pain and inflammation, with gender-specific implications.
- P2X4's involvement in multiple pathologies suggests its significant potential as a therapeutic target for conditions including pain, inflammation, and neurodegeneration.
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