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 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.
Schuiling
M
M
Department of Molecular Pharmacology, University Centre for Pharmacy, Groningen, The Netherlands.
Zuidhof
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AB
Meurs
H
H
Zaagsma
J
J
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001549:Benzamides / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D016084:Bronchoconstriction / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000502:physiology*
D000485:Allergens; D001549:Benzamides; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C073839:SR 48968; D006632:Histamine