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Effect of Tachykinins on Airway Function in Cynomolgus Monkeys

Pulmonary Pharmacology & Therapeutics
Publication Date
DOI: 10.1006/pupt.2001.0278
  • Monkeys
  • Neurokinin A
  • Substance P
  • Airway.
  • Physics


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. NK 1-(CP 99,994) and NK 2-(SR 48968) receptor antagonists were used to evaluate the role of NK 1and NK 2receptors on responses to NKA and SP. Lung resistance (R L) and dynamic lung compliance (C Dyn) 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 R Land C Dynwhereas aerosolized histamine (0.01–1 mg/ml) dose-dependently increased R Land decreased C Dyn. Intravenous NKA (1–100 μg/kg), SP (1–30 μg/kg) or histamine (1–100 μg/kg) increased R Land decreased C Dyn. 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 NK 1and NK 2receptors are involved in the bronchonconstrictor response to exogenously administered tachykinins in cynomolgus monkeys.

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