Role of tachykinin NK 2 ‐receptor activation in the allergen‐induced late asthmatic reaction, airway hyperreactivity and airway inflammatory cell influx in conscious, unrestrained guinea‐pigs

In a guinea‐pig model of allergic asthma, we investigated the involvement of the tachykinin NK 2 receptors in allergen‐induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions and inflammatory cell influx in the airways, using the selective non‐peptide NK 2 receptor antagonist SR48968. On two different occasions, separated by a 1 week interval, ovalbumin (OA)‐sensitized guinea‐pigs inhaled either vehicle (3 min) or SR48968 (100 n M , 3 min) at 30 min before as well as at 5.5 h after OA provocation (between the EAR and LAR) in a random crossover design. SR48968 had no significant effect on the EAR, but significantly attenuated the LAR by 44.2±16.4% ( P <0.05) compared to saline control. The NK 2 receptor antagonist did not affect the OA‐induced AHR to histamine after the EAR at 5 h after OA challenge (3.59±0.59 fold increase in histamine reactivity vs 3.79±0.61 fold increase in the controls, NS), but significantly reduced the AHR after the LAR at 23 h after OA challenge (1.59±0.24 fold increase vs 1.93±0.15 fold increase, respectively, P <0.05). Bronchoalveolar lavage studies performed at 25 h after the second OA provocation showed that SR48968 significantly inhibited the allergen‐induced infiltration of neutrophils ( P <0.05) and lymphocytes ( P <0.01) in the airways. These results indicate that NK 2 receptor activation is importantly involved in the development of the allergen‐induced late (but not early) asthmatic reaction and late (but not early) AHR to histamine, and that NK 2 receptor‐mediated infiltration of neutrophils and lymphocytes in the airways may contribute to these effects.British Journal of Pharmacology (1999) 127 , 1030–1038; doi: 10.1038/sj.bjp.0702628