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The involvement of sensory neuropeptides in toluene diisocyanate‐induced tracheal hyperreactivity in the mouse airways
Author(s) -
Scheerens Heleen,
Buckley Theresa L.,
Muis Thea,
Loveren Henk,
Nijkamp Frans P.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16087.x
Subject(s) - substance p , neurokinin a , neuropeptide , sensitization , capsaicin , medicine , neurogenic inflammation , sensory system , antagonist , receptor , endocrinology , immunology , biology , neuroscience
1 Recently, we developed a murine model to investigate toluene diisocyanate (TDI)‐induced occupational asthma. After skin‐sensitization and intranasal challenge with TDI (1%) mice exhibited tracheal hyperreactivity 24 h after the challenge. 2 The aim of the present study was to investigate the possible role for sensory neuropeptides in the development of this tracheal hyperreactivity. 3 First, we demonstrated that direct application of TDI in vitro induced the release of tachykinins from the sensory nerves in the mouse isolated trachea. Second, capsaicin pretreatment, resulting in the depletion of sensory neuropeptides, completely abolished the TDI‐induced tracheal hyperreactivity 24 h after the challenge. Third, the selective neurokinin 1 (NK 1 )‐receptor antagonist RP 67580 (0.2 μmol kg −1 ) also inhibited tracheal hyperreactivity when it was administered before the challenge. However, administration of RP 67580 during the sensitization phase did not result in a suppression of the TDI‐induced tracheal hyperreactivity 24 after the challenge. 4 When TDI‐sensitized mice were topically challenged with TDI a marked ear swelling response was observed. The cutaneous response after TDI application was not affected by capsaicin pretreatment or RP 67580 administration. 5 These results clearly show that sensory neuropeptides, particularly tachykinins, are essential for the development of TDI‐induced tracheal hyperreactivity during the effector phase. The differences between the airways and skin with respect to the sensory neuropeptides is intriguing and could suggest a local action for the tachykinins in the airways.