Role of tachykinin NK₂-receptor activation in the allergen-induced late asthmatic reaction, airway hyperreactivity and airway inflammatory cell influx in conscious, unrestrained guinea-pigs

1 In a guinea-pig model of allergic asthma, we investigated the involvement of the tachykinin NK2 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 NK2 receptor antagonist SR48968.

2 On two different occasions, separated by a 1 week interval, ovalbumin (OA)-sensitized guineapigs inhaled either vehicle (3 min) or SR48968 (100 nM, 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.

3 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.

4 The NK2 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 after OA challenge (1.59 +/- 0.24 fold increase vs 1.93 +/- 0.15 fold increase, respectively, P <0.05).

5 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.

6 These results indicate that NK2 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 NK2 receptor-mediated infiltration of neutrophils and lymphocytes in the airways may contribute to these effects.