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Research Article Free access | 10.1172/JCI114236

Recombinant human enkephalinase (neutral endopeptidase) prevents cough induced by tachykinins in awake guinea pigs.

H Kohrogi, J A Nadel, B Malfroy, C Gorman, R Bridenbaugh, J S Patton, and D B Borson

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 September 1, 1989 - More info

Published in Volume 84, Issue 3 on September 1, 1989
J Clin Invest. 1989;84(3):781–786. https://doi.org/10.1172/JCI114236.
© 1989 The American Society for Clinical Investigation
Published September 1, 1989 - Version history
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Abstract

To determine whether recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11) prevents cough induced by exogenously applied and endogenously released neuropeptides, we measured cough responses to aerosolized solutions of substance P or of capsaicin for 2 min in random-source guinea pigs before or after exposing them to aerosolized recombinant human enkephalinase. Substance P (10(-16) M) increased coughing compared with its vehicle. Enkephalinase (120 micrograms) inhibited cough induced by subsequent exposure to substance P compared with the response to substance P alone, but after further exposure to the enkephalinase inhibitor leucine-thiorphan (10(-5) M), substance P increased cough significantly. Similar results were obtained for capsaicin-induced cough. In pathogen-free guinea pigs, after they inhaled inactive recombinant enkephalinase (33 micrograms), capsaicin (10(-13) M) increased cough significantly. In contrast, after they inhaled active recombinant enkephalinase (33 micrograms), capsaicin increased cough only slightly. These results suggest that aerosolized enkephalinase reaches the sites of release or actions of endogenous neuropeptides and, by degrading them, prevents cough induced by their release. Furthermore, these studies suggest that recombinant enkephalinase might be useful in the treatment of cough and other symptoms of diseases involving peptides cleaved by this enzyme.

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