Comparison of TRPA1-versus TRPV1-mediated cough in guinea pigs

Mariana Brozmanova, Lenka Mazurova, Fei Ru, Milos Tatar, Marian Kollarik

Research output: Contribution to journalArticlepeer-review

Abstract

TRPA1 receptor is activated by endogenous inflammatory mediators and exogenous pollutant molecules relevant to respiratory diseases. Previous studies have implicated TRPA1 as a drug target for antitussive therapy. Here we evaluated the relative efficacy of TRPA1 activation to evoke cough. In conscious guinea pigs the TRPA1 agonist allyl-isothiocyanate (AITC) evoked cough with a maximally effective concentration of 10 mM that was abolished by the selective TRPA1 antagonist AP-18. AITC (10 mM) was approximately 3-times less effective in inducing cough than capsaicin (50 μM). Ex vivo single fiber extracellular recordings revealed that, similarly to capsaicin, AITC evoked activation in airway jugular C-fibers, but not in airway nodose Aδ-fibers. Consistent with the cough studies, AITC was approximately 3-times less effective than capsaicin in evoking sustained activation of the jugular C-fibers. Another TRPA1 agonist, cinnamaldehyde, was approximately twofold more effective than AITC in inducing cough. However, the cinnamaldehyde (10 mM)-induced cough was only partially inhibited by the TRPA1 antagonist AP-18, and was abolished by combination of AP-18 and the TRPV1 antagonist I-RTX. We conclude that in naïve guinea pigs, TRPA1 activation initiates cough that is relatively modest compared to the cough initiated by TRPV1, likely due to lower efficacy of TRPA1 stimulation to induce sustained activation of airway C-fibers.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalEuropean Journal of Pharmacology
Volume689
Issue number1-3
DOIs
StatePublished - Aug 15 2012

Keywords

  • Airway C-fiber
  • Allyl-isothiocyanate
  • Capsaicin
  • Cinnamaldehyde
  • Cough
  • TRPA1
  • TRPV1
  • Vagus nerve

ASJC Scopus subject areas

  • Pharmacology

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