ArticleThe Journal of allergy and clinical immunology2016
Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.
Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.Respiratory research · 2023Pooled it
- Heterogeneity of cough hypersensitivity mediated by TRPV1 and TRPA1 in patients with chronic refractory cough.Respiratory research · 2019Trial
- Physiological mechanisms and therapeutic targets in chronic cough.Physiological reports · 2026Review
- Transient receptor potential vanilloid 4 channels contribute to the initiation of water-induced swallowing reflexes.Scientific reports · 2026Article
- TRPV4-Mast Cell Interactions in Neurogenic Inflammation and Chronic Diseases: A Narrative Review.International journal of molecular sciences · 2026Review
- Transient receptor potential vanilloid 4 channels contribute to the initiation of water-induced swallowing reflexes.Research square · 2026Article
- From respiratory viral infection to persistent cough hypersensitivity: neuroimmune regulation and therapeutic implications of P2X3/TRP ion-channel targets.Frontiers in pharmacology · 2026Review
- Research Progress on Upper Airway Cough Syndrome.World journal of otorhinolaryngology - head and neck surgery · 2025Review
- Reflex regulation of respiration and heart rate by inhaled activators of vagal bronchopulmonary afferents.Journal of neurophysiology · 2025Article
- Unmet need for biomarkers in chronic cough: a review of current challenges and future directions.ERJ open research · 2025Review
- Activation of Adenosine Triphosphate-Gated Purinergic 2 Receptor Channels by Transient Receptor Potential Vanilloid Subtype 4 in Cough Hypersensitivity.Biomolecules · 2025Article
- Targeting P2X Receptors-Current Progress in Sepsis.International journal of inflammation · 2025Review
- Article
- The Therapeutic Landscape in Chronic Cough.Lung · 2024Review
- Neural Mechanisms Underlying the Coughing Reflex.Neuroscience bulletin · 2023Review
- Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis.EClinicalMedicine · 2023Article
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- ERS International Congress 2022: highlights from the Airway Diseases Assembly.ERJ open research · 2023Review
- Unconventional interactions of the TRPV4 ion channel with beta-adrenergic receptor ligands.Life science alliance · 2023Article
- Novel trehalose-based excipients for stabilizing nebulized anti-SARS-CoV-2 antibody.International journal of pharmaceutics · 2023Article
2 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
14 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.
objectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.
methodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.
resultsHere we show TRPV4-induced activation of guinea pig airway-specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.
conclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP-mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.
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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.