Neutral endopeptidase-like enzyme controls the contractile activity of substance P in guinea pig lung.
The responsiveness of isolated guinea pig lung parenchymal strips to substance P was enhanced by at least 100-fold in the presence of the endopeptidase inhibitors phosphoramidon (1 microM) or thiorphan (1 microM), but not with the converting enzyme inhibitor, captopril, or an inhibitor of serum carboxypeptidase N (both 1 microM). Responses of guinea pig tracheal rings to substance P were also markedly potentiated by phosphoramidon. The increase in tissue responsiveness by these inhibitors was relatively specific for substance P among several other spasmogenic peptides, including formyl-methionyl-leucyl-phenylalanine and the complement peptides C3a and C5a. The enhanced responses appear to result from a decrease in the rate of substance P degradation in the presence of neutral endopeptidase inhibitors. Specific binding of substance P to its receptor on bronchial membranes was increased by three- to fourfold in the presence of phosphoramidon. These data demonstrate an enhanced potential for substance P to contract lung tissues when degradation by a neutral endopeptidase-like enzyme is blocked.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003176:Complement C3 / Q000494:pharmacology; D015926:Complement C3a; D003182:Complement C5 / Q000494:pharmacology; D015936:Complement C5a; D004347:Drug Interactions; D010450:Endopeptidases / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung; D009119:Muscle Contraction / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea
D000806:Angiotensin-Converting Enzyme Inhibitors; D003176:Complement C3; D003182:Complement C5; D006020:Glycopeptides; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015926:Complement C3a; D015936:Complement C5a; D002216:Captopril; D015244:Thiorphan; D008625:Tiopronin; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; C008890:phosphoramidon