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.

Abstract

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 guinea-pigs 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 h 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.

• Authors: M Schuiling, A B Zuidhof, H Meurs, J Zaagsma
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 127 Issue 4 Pg. 1030-8 (Jun 1999) ISSN: 0007-1188 [Print] England
• PMID: 10433512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Benzamides
• Piperidines
• Receptors, Neurokinin-2
• SR 48968
• Histamine

Topics

• Allergens (immunology)
• Animals
• Asthma (physiopathology)
• Benzamides (pharmacology)
• Bronchial Hyperreactivity (etiology)
• Bronchoconstriction (drug effects)
• Female
• Guinea Pigs
• Histamine (pharmacology)
• Inflammation (etiology)
• Lymphocytes (physiology)
• Male
• Neutrophils (physiology)
• Piperidines (pharmacology)
• Receptors, Neurokinin-2 (physiology)