RT Journal Article
SR Electronic
T1 Transient receptor potential ankyrin 1 (TRPA1)-mediated cough
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p840
VO 38
IS Suppl 55
A1 Mariana Brozmanova
A1 Lenka Mazurova
A1 Fei Ru
A1 Milos Tatar
A1 Marian Kollarik
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p840.abstract
AB TRPA1 detects many endogenous inflammatory and environmental pollutant molecules. Previous studies implicated TRPA1 as a drug target for antitussive therapy. We evaluated relative efficacy of the TRPA1 activation in inducing cough in guinea pigs. Inhalation of the TRPA1 agonist allyl-isothiocyanate (AITC) evoked cough with a maximally effective concentration of 10mM (2.8±0.8 coughs/5min above vehicle, n=12) that was abolished by the TRPA1 selective antagonist AP-18 (1mM, n=8). AITC was ∼3-times less effective in inducing cough than the TRPV1 agonist capsaicin in the sub-maximally effective selective concentration (50μM) (8.2±2.1 coughs/5min above vehicle, n=9, p<0.05). Ex vivo single fiber recordings showed that AITC was ∼3-times less effective than capsaicin in evoking sustained activation of the cough-triggering tracheal jugular C-fibers (65±18 [n=7] vs. 210±57 [n=7] maximum action potentials/30s bin, p<0.05). AITC failed to activate the capsaicin-insensitive tracheal nodose A-fibers (n=6). Another TRPA1 agonist cinnamaldehyde (10mM) was surprisingly ∼2-fold more effective than AITC in inducing cough (6.0±0.9 coughs/5min above vehicle, n=12, p<0.01). The cinnamaldehyde (10mM)-induced cough was only partially (by∼60%, n=8) inhibited by the TRPA1 antagonists AP-18 (1mM), but abolished by combination of AP-18 and the TRPV1 antagonist I-RTX (30μM, n=6). We conclude that in guinea pigs TRPA1 initiates cough that is relatively modest compared to cough initiated by TRPV1. This is likely due to lower efficacy of TRPA1 in inducing sustained activation of the cough-triggering C-fibers. Our data indicate that TRPV1 in addition to TRPA1 contributes to cough evoked by cinnamaldehyde in this species. Supported by CEVYPET (EU sources).