ArticleThe Journal of biological chemistry2016
Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.The journal of pain · 2024Article
- Blockage of HCN Channels Inhibits the Function of P2X Receptors in Rat Dorsal Root Ganglion Neurons.Neurochemical research · 2022Article
- Therapeutic Antibodies Targeting Potassium Ion Channels.Handbook of experimental pharmacology · 2021Article
- Production of TRPV2-targeting functional antibody ameliorating dilated cardiomyopathy and muscular dystrophy in animal models.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.British journal of pharmacology · 2019Article
- Antibodies and venom peptides: new modalities for ion channels.Nature reviews. Drug discovery · 2019Review
- Monoclonal Antibodies Targeting Ion Channels and Their Therapeutic Potential.Frontiers in pharmacology · 2019Review
- Using automated patch clamp electrophysiology platforms in pain-related ion channel research: insights from industry and academia.British journal of pharmacology · 2018Review
- Purinergic drug targets for gastrointestinal disorders.Current opinion in pharmacology · 2017Review
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
- Ocular Purine Receptors as Drug Targets in the Eye.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2016Review
- Merck stakes out 'irritable' neuron territory with $1.25 billion.Nature biotechnology · 2016Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purinergic homomeric P2X3 and heteromeric P2X2/3 receptors are ligand-gated cation channels activated by ATP. Both receptors are predominantly expressed in nociceptive sensory neurons, and an increase in extracellular ATP concentration under pathological conditions, such as tissue damage or visceral distension, induces channel opening, membrane depolarization, and initiation of pain signaling. Hence, these receptors are considered important therapeutic targets for pain management, and development of selective antagonists is currently progressing. To advance the search for novel analgesics, we have generated a panel of monoclonal antibodies directed against human P2X3 (hP2X3). We have found that these antibodies produce distinct functional effects, depending on the homomeric or heteromeric composition of the target, its kinetic state, and the duration of antibody exposure. The most potent antibody, 12D4, showed an estimated IC50 of 16 nm on hP2X3 after short term exposure (up to 18 min), binding to the inactivated state of the channel to inhibit activity. By contrast, with the same short term application, 12D4 potentiated the slow inactivating current mediated by the heteromeric hP2X2/3 channel. Extending the duration of exposure to ∼20 h resulted in a profound inhibition of both homomeric hP2X3 and heteromeric hP2X2/3 receptors, an effect mediated by efficient antibody-induced internalization of the channel from the plasma membrane. The therapeutic potential of mAb12D4 was assessed in the formalin, complete Freund's adjuvant, and visceral pain models. The efficacy of 12D4 in the visceral hypersensitivity model indicates that antibodies against P2X3 may have therapeutic potential in visceral pain indications.
Indexed as
Identifiers
What OpenQuestion holds
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.