PHOSPHORAMIDON POTENTIATES THE BRONCHOCONSTRICTION INDUCED BY INHALEDBOMBESIN IN GUINEA-PIGS

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 (0.0 1 or 0.1 mg/ml) induced a dose-dependent increase in pulmonary inflati on pressure. Pretreatment of the guinea-pigs with phosphoramidon (0.1 mM), administered by aerosol for 15 min, 15 min prior to challenge, ma rkedly potentiated the increase in pulmonary inflation pressure induce d by bombesin (0.01 mg/ml) and subtance P (0.1 mg/ml). This result sug gests a local hydrolysis of bombesin by airway neutral endopeptidase r educing the activity of this peptide on smooth muscle.