Evidence map›Paper›PMID 22693178›Full record

ArticleThorax2012

Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin.

Megan Grace, Mark A Birrell, Eric Dubuis, Sarah A Maher, Maria G Belvisi

Open access · hybridAbstract read
In one paragraph

Article in Thorax, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Modulation of TRPV-1 by prostaglandin-EScientific reports · 2020
    Trial
  6. Sesquiterpene Lactone Derivatives ofPharmaceuticals (Basel, Switzerland) · 2026
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Research Progress on Upper Airway Cough Syndrome.World journal of otorhinolaryngology - head and neck surgery · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Research Progress on TRPA1 in Diseases.The Journal of membrane biology · 2023
    Review
  17. Article
  18. Article
  19. Review
  20. Review

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Megan GraceRespiratory Pharmacology Group, Pharmacology and Toxicology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Mark A Birrell
Eric Dubuis
Sarah A Maher
Maria G Belvisi
Imperial College London · GBUniversity of Manchester · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E52708X/1Department of HealthMedical Research Council G0800195Medical Research Council G0800196Medical Research Council G1000758Wellcome Trust 089301/Z/09/Z
6 · The paper itself

Abstract

backgroundCough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and a recent meta-analysis concluded that over-the-counter remedies are ineffective and there is increasing concern about their use in children. Endogenous inflammatory mediators such as prostaglandin E2 (PGE2) and bradykinin (BK), which are often elevated in respiratory disease states, are also known to cause cough by stimulating airway sensory nerves. However, how this occurs is not understood.

methodsWe hypothesised that the transient receptor potential (TRP) channels, TRPA1 and TRPV1, may have a role as 'common effectors' of tussive responses to these agents. We have employed a range of in vitro imaging and isolated tissue assays in human, murine and guinea pig tissue and an in vivo cough model to support this hypothesis.

resultsUsing calcium imaging we demonstrated that PGE2 and BK activated isolated guinea pig sensory ganglia and evoked depolarisation (activation) of vagal sensory nerves, which was inhibited by TRPA1 and TRPV1 blockers (JNJ17203212 and HC-030031). These data were confirmed in vagal sensory nerves from TRPA1 and TRPV1 gene deleted mice. TRPV1 and TRPA1 blockers partially inhibited the tussive response to PGE2 and BK with a complete inhibition obtained in the presence of both antagonists together in a guinea pig conscious cough model.

conclusionThis study identifies TRPA1 and TRPV1 channels as key regulators of tussive responses elicited by endogenous and exogenous agents, making them the most promising targets currently identified in the development of anti-tussive drugs.

Indexed as

AcroleinAdultAgedAnimalsAntitussive AgentsBradykininCalciumCapsaicinCoughDinoprostoneFemaleGuinea PigsHumansMaleMiceMice, Inbred C57BLAcroleinAntitussive AgentsBradykininCalciumCapsaicinDinoprostoneTransient Receptor Potential Channels

Identifiers

PMID22693178
PMCPMC3446777
OpenAlexW2165913798

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.