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The effect of the neutral endopeptidase inhibitor, phosphoramidon, on the bronchoconstriction induced by aerosolized bombesin in the guinea pig was investigated. Administered by aerosol for 1 min, bombesin (0.01 or 0.1 mg/ml) induced a dose-dependent increase in pulmonary inflation pressure. Pretreatment of the guinea-pigs with phosphoramidon (0.1 mM), administered by aerosol for 15 min, 15 min prior to challenge, markedly potentiated the increase in pulmonary inflation pressure induced by bombesin (0.01 mg/ml) and substance P (0.1 mg/ml). This result suggests a local hydrolysis of bombesin by airway neutral endopeptidase reducing the activity of this peptide on smooth muscle.
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