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Research Article Free access | 10.1172/JCI117594

Cationic protein-induced sensory nerve activation: role of substance P in airway hyperresponsiveness and plasma protein extravasation.

A J Coyle, F Perretti, S Manzini, and C G Irvin

Department of Medicine, University of Colorado Health Science Center, Denver.

Find articles by Coyle, A. in: PubMed | Google Scholar

Department of Medicine, University of Colorado Health Science Center, Denver.

Find articles by Perretti, F. in: PubMed | Google Scholar

Department of Medicine, University of Colorado Health Science Center, Denver.

Find articles by Manzini, S. in: PubMed | Google Scholar

Department of Medicine, University of Colorado Health Science Center, Denver.

Find articles by Irvin, C. in: PubMed | Google Scholar

Published December 1, 1994 - More info

Published in Volume 94, Issue 6 on December 1, 1994
J Clin Invest. 1994;94(6):2301–2306. https://doi.org/10.1172/JCI117594.
© 1994 The American Society for Clinical Investigation
Published December 1, 1994 - Version history
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Abstract

We have previously reported that human eosinophil granule major basic protein and synthetic cationic proteins such as poly-L-arginine and poly-L-lysine, can increase airway responsiveness in vivo. In the present study, we have investigated whether activation of sensory C-fibers is important in this phenomenon. Dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of poly-L-lysine in anaesthetized spontaneously breathing rats, and the concentration of methacholine required to induce a doubling in total lung resistance was calculated. Poly-L-lysine induced a fivefold increase in airway responsiveness, which was inhibited by neonatal capsaicin treatment and potentiated by phosphoramidon (100 micrograms/ml). Furthermore, pretreatment with either CP, 96-345, or RP-67580 two selective NK-1 receptor antagonists inhibited poly-L-lysine-induced airway hyperresponsiveness and plasma protein extravasation. In vitro, cationic proteins stimulated the release of calcitonin gene-related peptide-like immunoreactivity from perfused slices of the main bronchi. Our results demonstrate that cationic proteins can activate sensory C-fibers in the airways, an effect which is important in the subsequent development of airway hyperresponsiveness and plasma protein extravasation. Cationic proteins may therefore function as a link between inflammatory cell accumulation and sensory nerve activation.

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