Sch 37224, an Experimental Antiallergy Compound, Inhibits the Neuropeptide Component of Hyperventilation- and Nicotine-Induced Bronchoconstriction in Guinea Pigs
作者:
Peter J. Mauser,
Caroline Rasquinha,
John A. Hey,
William Kreutner,
Robert W. Egan,
Joseph E. Sherwood,
John Anthes,
Scott Greenfeder,
Richard W. Chapman,
期刊:
Pharmacology
(Karger Available online 1997)
卷期:
Volume 54,
issue 1
页码: 8-15
ISSN:0031-7012
年代: 1997
DOI:10.1159/000139464
出版商: S. Karger AG
关键词: Sch 37224;Bronchospasm;Hyperventilation;Nicotine;Tachykinins;Guinea pigs
数据来源: Karger
摘要:
Sch 37224 is an experimental antiallergy coumpound that inhibits hyperventilation-induced bronchoconstriction (HIB) in guinea pigs and cold air bronchospasm in human asthmatics. HIB in guinea pigs may involve the release of tachykinins, such as neurokinin A (NKA) and substance P (SP), and the action of Sch 37224 in this model may relate to inhibition of these neuropeptides. We studied the effect of Sch 37224 on the neuropeptide component of HIB that was enhanced in guinea pigs treated with the neutral endopeptidase inhibitors, thiorphan and phosphoramidon. Pulmonary resistance (RL) and dynamic lung compliance (Coyn) were measured in anesthetized, mechanically ventilated guinea pigs. RL and CDyn were measured at baseline (1 ml/l00 g tidal volume and 50 breaths/min) and after a 10-min period of hyperventilation (1 ml/l00 g, 150 breaths/min). Hyperventilation produced modest changes in RL (+41 ± 12%) and Coyn (–12 ± 3%) which were markedly enhanced by treatment with 3 mg/kg of either thiorphan or phosphoramidon (Rl + 269 ± 43% for thiorphan, + 292 ± 63% for phosphoramidon and Coyn70%) with 5 mg/kg, p.o., of Sch 37224. In other studies, the peptidergic (conducted in the presence of ipratropium bromide and phosphoramidon) bronchoconstrictor response to intravenous nicotine (1 mg/kg) was also inhibited by Sch 37224 (0.3-10 mg/kg, p.o.). However, Sch 37224 (5 mg/kg, p.o.) had no effect on the bronchoconstrictor response to intravenous NKA. These results indicate that Sch 37224 inhibits the neuropeptide component of HIB and nicotine in guinea pigs and this effect appears to be mediated by the inhibition of the release of tachykinins from airway
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