Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

H Kohrogi; P D Graf; K Sekizawa; D B Borson; J A Nadel

doi:10.1172/JCI113827

Cardiovascular Research Institute, University of California, San Francisco 94143.

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Cardiovascular Research Institute, University of California, San Francisco 94143.

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Cardiovascular Research Institute, University of California, San Francisco 94143.

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Cardiovascular Research Institute, University of California, San Francisco 94143.

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Cardiovascular Research Institute, University of California, San Francisco 94143.

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Published in Volume 82, Issue 6 on December 1, 1988
J Clin Invest. 1988;82(6):2063–2068. https://doi.org/10.1172/JCI113827.
© 1988 The American Society for Clinical Investigation

Published December 1, 1988 - Version history

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.