RT Journal Article
SR Electronic
T1 Late asthmatic response is modulated by TRPA1 antagonists in ovalbumin-induced bronchoconstriction in anaesthetized guinea pigs
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2803
VO 40
IS Suppl 56
A1 Thierry Bouyssou
A1 Zoe Noakes
A1 Silke Hobbie
A1 Martin Fleck
A1 Andreas Schnapp
A1 Florian Gantner
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/2803.abstract
AB In animal models of asthma, ovalbumin (OVA) aerosol results in bronchoconstriction characterized by a histamine-related early asthmatic response (EAR) followed by a neuropeptide-related late asthmatic response (LAR) which can be modulated by transient receptor potential (TRP) channel A1 antagonists (Thorax. 2012, 67, 19-25).The aim of the study was to assess the potential of two TRPA1 antagonists on the EAR and LAR in OVA-induced bronchoconstriction in anaesthetized guinea pigs.Bronchoconstriction was induced by intra-tracheal administration of a single dose of OVA (50 µg/kg) and lung resistance recorded for 30 minutes. The animals were pre-treated with pyrilamine (2 mg/kg i.v.) or its vehicle (saline) 10 min before OVA. The TRPA1 antagonists HC-030031 and A-967079 or their vehicle (0.5 % methylcellulose) were administered i.p. 1 h before OVA. Without pyrilamine pre-treatment, OVA induced a fast increase in lung resistance (max. 60 ± 13 ml overflow after 1 min) which was not reduced by the TRPA1 antagonists. Under pyrilamine pre-treatment, OVA induced a slow increase in lung resistance (max. 33 ± 10 ml overflow at the end of the recording). HC-030031 (1 µg/kg – 1 mg/kg) dose-dependently inhibited the non-histamine-related OVA- induced bronchoconstriction (ED50 = 0.01 mg/kg) with a maximum bronchoprotection of 76 % at 0.03 mg/kg (p<0.05). A-967079 (1 µg/kg – 1 mg/kg) displayed the same profile as HC-030031 (ED50 = 0.01 mg/kg) with a maximum bronchoprotection of 78 % at 0.03 mg/kg (p<0.05).This study shows that the EAR is histamine related, while the LAR is modulated by the TRPA1 channel in OVA-induced bronchoconstriction in anaesthetized guinea pigs.