THE INVOLVEMENT OF SENSORY NEUROPEPTIDES IN TOLUENE DIISOCYANATE-INDUCED TRACHEAL HYPERREACTIVITY IN THE MOUSE AIRWAYS

1 Recently, we developed a murine model to investigate toluene diisocy anate (TDI)-induced occupational asthma. After skin-sensitization and intranasal challenge with TDI (1%) mice exhibited tracheal hyperreacti vity 24 h after the challenge. 2 The aim of the present study was to i nvestigate the possible role for sensory neuropeptides in the developm ent of this tracheal hyperreactivity. 3 First, we demonstrated that di rect application of TDI in vitro induced the release of tachykinins fr om the sensory nerves in the mouse isolated trachea. Second, capsaicin pretreatment, resulting in the depletion of sensory neuropeptides, co mpletely abolished the TDI-induced tracheal hyperreactivity 24 h after the challenge. Third, the selective neurokinin(1) (NK1)-receptor anta gonist RP 67580 (0.2 mu mol kg(-1)) also inhibited tracheal hyperreact ivity when it was administered before the challenge. However, administ ration of RP 67580 during the sensitization phase did not result in a suppression of the TDI-induced tracheal hyperreactivity 24 after the c hallenge. 4 When TDI-sensitized mice were topically challenged with TD I 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 neuro peptides, 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 t achykinins in the airways.