ArticlePloS one2014
Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 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
- Wired for immunity: neuroimmune control of the lung by sensory neurons.Nature reviews. Neuroscience · 2026Review
- Transient Receptor Potential (TRP) Channels as Fundamental Regulators of Fibrosis and Pruritus-A New Therapeutic Target for Pathological Scar Management.International journal of molecular sciences · 2026Review
- Unraveling the neuro-immune axis in cough hypersensitivity: from pathogenesis to synergistic management.Frontiers in medicine · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- The TRPA1 cation channel is upregulated by cigarette smoke in mouse and human macrophages modulating lung inflammation.Scientific reports · 2025Article
- Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel.ChemMedChem · 2025Article
- The Therapeutic Landscape in Chronic Cough.Lung · 2024Review
- Transient Receptor Potential Ankyrin 1 (TRPA1) Mediated LPS-Induced Inflammation in Periodontal Ligament Stem Cells by Inhibiting the Phosphorylation of JNK.Stem cells international · 2024Article
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Review
- The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.Pulmonary therapy · 2022Article
- Advances in TRP channel drug discovery: from target validation to clinical studies.Nature reviews. Drug discovery · 2022Review
- Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker.British journal of pharmacology · 2021Article
- TRP channels in airway sensory nerves.Neuroscience letters · 2021Review
- Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough.Clinical pharmacology and therapeutics · 2021Review
- Update on Calcium Signaling in Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1) is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca(+2) influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1.
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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.