ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Use-dependent inhibition of P2X3 receptors by nanomolar agonist.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Generalised Hodgkin-Huxley model captures human P2X and AMPA receptor currents.The Journal of physiology · 2026Article
- Subtype-Specific Ligand Binding and Activation Gating in Homomeric and Heteromeric P2X Receptors.Biomolecules · 2024Article
- Role of ATP in migraine mechanisms: focus on P2X3 receptors.The journal of headache and pain · 2023Review
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Modeling a Nociceptive Neuro-Immune Synapse Activated by ATP and 5-HT in Meninges: Novel Clues on Transduction of Chemical Signals Into Persistent or Rhythmic Neuronal Firing.Frontiers in cellular neuroscience · 2020Article
- Anticancer, antimicrobial, and analgesic activities of spider venoms.Toxicology research · 2018Review
- Mechanistic insights from resolving ligand-dependent kinetics of conformational changes at ATP-gated P2X1R ion channels.Scientific reports · 2016Article
- Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies.The Journal of biological chemistry · 2016Article
- Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain.Molecular pain · 2016Article
- Molecular mechanism for opioid dichotomy: bidirectional effect of μ-opioid receptors on P2X₃ receptor currents in rat sensory neurones.Purinergic signalling · 2015Article
- The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.Science translational medicine · 2015Article
- Putative roles of purinergic signaling in human immunodeficiency virus-1 infection.Biology direct · 2014Article
- Subtype-specific mechanisms for functional interaction between α6β4* nicotinic acetylcholine receptors and P2X receptors.Molecular pharmacology · 2014Article
- Desensitization properties of P2X3 receptors shaping pain signaling.Frontiers in cellular neuroscience · 2013Review
- P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions.The Journal of biological chemistry · 2013Article
- Molecular and functional properties of P2X receptors--recent progress and persisting challenges.Purinergic signalling · 2012Review
- Activation and regulation of purinergic P2X receptor channels.Pharmacological reviews · 2011Review
- Sensing muscle ischemia: coincident detection of acid and ATP via interplay of two ion channels.Neuron · 2010Article
- Structural interpretation of P2X receptor mutagenesis studies on drug action.British journal of pharmacology · 2010Review
- Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.Molecular pain · 2008Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2X3 receptors desensitize within 100 ms of channel activation, yet recovery from desensitization requires several minutes. The molecular basis for this slow rate of recovery is unknown. We designed experiments to test the hypothesis that this slow recovery is attributable to the high affinity (< 1 nM) of desensitized P2X3 receptors for agonist. We found that agonist binding to the desensitized state provided a mechanism for potent inhibition of P2X3 current. Sustained applications of 0.5 nM ATP inhibited > 50% of current to repetitive applications of P2X3 agonist. Inhibition occurred at 1000-fold lower agonist concentrations than required for channel activation and showed strong use dependence. No inhibition occurred without previous activation and desensitization. Our data are consistent with a model whereby inhibition of P2X3 by nanomolar [agonist] occurs by the rebinding of agonist to desensitized channels before recovery from desensitization. For several ATP analogs, the concentration required to inhibit P2X3 current inversely correlated with the rate of recovery from desensitization. This indicates that the affinity of the desensitized state and recovery rate primarily depend on the rate of agonist unbinding. Consistent with this hypothesis, unbinding of [32P]ATP from desensitized P2X3 receptors mirrored the rate of recovery from desensitization. As expected, disruption of agonist binding by site-directed mutagenesis increased the IC50 for inhibition and increased the rate of recovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.