1. Effect of Tachykinins on Airway Function in Cynomolgus Monkeys
- Author
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Mauser, P.J., Skeans, S., Ritacco, G., Fernandez, X., House, A., and Chapman, R.W.
- Abstract
Tachykinins have been implicated as important mediators of asthma. This study used neurokinin A (NKA) and substance P (SP) to evaluate the effect of tachykinins on airway mechanics in cynomolgus monkeys. NK1-(CP 99,994) and NK2-(SR 48968) receptor antagonists were used to evaluate the role of NK1and NK2receptors on responses to NKA and SP. Lung resistance (RL) and dynamic lung compliance (CDyn) were measured in anesthetized, mechanically ventilated cynomolgus monkeys following aerosol or intravenous challenge with NKA, SP or the standard bronchoconstrictor, histamine. Inhaled NKA or SP had variable effects on RLand CDynwhereas aerosolized histamine (0.01–1 mg/ml) dose-dependently increased RLand decreased CDyn. Intravenous NKA (1–100 μg/kg), SP (1–30 μg/kg) or histamine (1–100 μg/kg) increased RLand decreased CDyn. Pretreatment with SR 48968 (0.1 and 1 mg/kg, iv) blocked bronchoconstrictor responses to iv NKA, whereas CP 99,994 (0.1 and 1 mg/kg, iv) was without effect. Bronchoconstrictor responses to iv SP were partially blocked by SR 48968 and CP 99,994. In conclusion, both NKA and SP produce bronchonconstriction in cynomolgus monkeys and this effect is more pronounced when they are given by the iv route. Furthermore, both NK1and NK2receptors are involved in the bronchonconstrictor response to exogenously administered tachykinins in cynomolgus monkeys.
- Published
- 2001
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