The involvement of sensory neuropeptides in toluene diisocyanate-induced tracheal hyperreactivity in the mouse airways

British Journal of Pharmacology
H ScheerensF P Nijkamp

Abstract

1. Recently, we developed a murine model to investigate toluene diisocyanate (%DI)-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 neurokinin1 (NK1)-receptor antagonist RP 67580 (0.2 mumol 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 pretre...Continue Reading

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Citations

Oct 18, 2000·European Journal of Pharmacology·A D KraneveldF P Nijkamp
Feb 7, 2002·Neurotoxicology·B Verones, M Oortgiesen
Jul 1, 2002·Environmental Toxicology and Pharmacology·Anneke H van HouwelingenFrans P Nijkamp
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