The involvement of sensory neuropeptides in toluene diisocyanate-induced tracheal hyperreactivity in the mouse airways
| Autor: | Theresa L. Buckley, Heleen Scheerens, Thea Muis, Frans P. Nijkamp, Henk Van Loveren |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Indoles Calcitonin Gene-Related Peptide Neuropeptide Substance P Isoindoles Calcitonin gene-related peptide Pharmacology Mice chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Isometric Contraction Tachykinins Respiratory Hypersensitivity Animals Medicine Neurons Afferent Respiratory system Sensitization Skin Mice Inbred BALB C Tracheal Diseases Toluene diisocyanate business.industry Neuropeptides respiratory system medicine.anatomical_structure chemistry Capsaicin Immunology Nasal administration Toluene 2 4-Diisocyanate business Research Article |
| Zdroj: | British Journal of Pharmacology. 119:1665-1671 |
| ISSN: | 0007-1188 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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