Involvement of a phosphoramidon-sensitive endopeptidase in the processing of big endothelin-1 in the guinea-pig.

摘要: Abstract In anaesthetized and ventilated guinea-pigs, i.v. injection of 1 nmol/kg big endothelin-1 (big ET-1) did not evoke significant changes in pulmonary inflation pressure (PIP) mean arterial blood (MBP), whereas the same dose (ET-1) induced marked rapid bronchoconstrictor pressor responses. Administered at 10 nmol/kg, ET-1 provoked increases PIP MBP, which developed slowly were long-lasting as compared to those evoked by ET-1. When was incubated for 45 min 37°C with α-chymotrypsin (2 mU/nmol) or pepsin (1 μg/nmol) then injected into guinea-pigs responses observed, kinetics similar noted after administration The magnitude α-chymotrypsin- pepsin-treated that ET-1, enzymes. Injected 5 mg/kg, before challenge, phosphoramidon almost totally inhibited thiorphan (5 mg/kg) partially reduced increase exerted a minimal effect on MBP. 20 mg/kg per os, h enalapril maleate captopril significantly alter bronchoconstriction hypertensive response peptide. present results indicate exhibits direct activities guinea-pig has be converted proteolytic enzymes full expression its activity. effects observed well inhibition treatment phosphoramidon, suggest peptide is metabolized vivo an active form neutral endopeptidase, metallopeptidase related it, involved this process.