Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.
To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase.
Kohrogi
H
H
Cardiovascular Research Institute, University of California, San Francisco 94143.
Graf
P D
PD
Sekizawa
K
K
Borson
D B
DB
Nadel
J A
JA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced*; D004357:Drug Synergism; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000494:pharmacology*; D015244:Thiorphan / Q000031:analogs & derivatives / Q000494:pharmacology
D006020:Glycopeptides; D013373:Substance P; C054498:leucine thiorphan; D015244:Thiorphan; D015260:Neprilysin; D002211:Capsaicin; C008890:phosphoramidon