ArticleThe Journal of physiology2005
P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 370 citations in OpenAlex.
- Efficacy and Safety of Ion Channel Modulators in Painful Diabetic Neuropathy.Diabetes, obesity & metabolism · 2026Pooled it
- An update and systematic review on drug therapies for the treatment of refractory chronic cough.Expert opinion on pharmacotherapy · 2018Pooled it
- Efficacy and safety of eliapixant in endometriosis-associated pelvic pain: the randomized, placebo-controlled phase 2b SCHUMANN study.BMC women's health · 2024Trial
- P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants.Clinical pharmacokinetics · 2024Trial
- First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: Tolerability, safety and pharmacokinetics.British journal of clinical pharmacology · 2022Trial
- Biomechanical regulation of bladder injury and repair.Nature reviews. Urology · 2026Review
- Functional characterization and classification of mechanosensitive bladder afferents.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- Cryo-EM structures of human P2X2/3 heteromer channel reveal the structural basis of ligand selectivity.Science advances · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.bioRxiv : the preprint server for biology · 2025Article
- Possible Roles for Purinergic Receptor P2RX4 in Breast and Prostate Cancers.International journal of molecular sciences · 2025Review
- Article
- Electroacupuncture improves cyclophosphamide-induced bladder overactivity by reducing mechanotransduction in the rat urothelium.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Targeting P2X Receptors-Current Progress in Sepsis.International journal of inflammation · 2025Review
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.The journal of pain · 2024Article
- Mass Balance and Metabolic Pathways of Eliapixant, a P2X3 Receptor Antagonist, in Healthy Male Volunteers.European journal of drug metabolism and pharmacokinetics · 2024Article
- Effect of pro-inflammatory cytokines on urothelial cell adenosine triphosphate release and breakdown.Bladder (San Francisco, Calif.) · 2024Article
- Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2023Review
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors variably composed of P2X2 and P2X3 subunits. P2X2 and P2X3 subunits can form homomultimeric P2X2, homomultimeric P2X3, or heteromultimeric P2X2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood. Here we describe null mutant mice lacking the P2X2 receptor subunit (P2X2-/-) and double mutant mice lacking both P2X2 and P2X3 subunits (P2X2/P2X3(Dbl-/-)), and compare these with previously characterized P2X3-/- mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG) neurones from wild-type mice responded to ATP with sustained inward currents, while dorsal root ganglia (DRG) neurones gave predominantly transient currents. Sensory neurones from P2X2-/- mice responded to ATP with only transient inward currents, while sympathetic neurones had barely detectable responses. Neurones from P2X2/P2X3(Dbl-/-) mice had minimal to no response to ATP. These data indicate that P2X receptors on sensory and sympathetic ganglion neurones involve almost exclusively P2X2 and P2X3 subunits. P2X2-/- and P2X2/P2X3(Dbl-/-) mice had reduced pain-related behaviours in response to intraplantar injection of formalin. Significantly, P2X3-/-, P2X2-/-, and P2X2/P2X3(Dbl-/-) mice had reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. No deficits in a wide variety of CNS behavioural tests were observed in P2X2-/- mice. Taken together, these data extend our findings for P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder.
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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.