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. 1994 Dec;94(6):2301–2306. doi: 10.1172/JCI117594

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

A J Coyle 1, F Perretti 1, S Manzini 1, C G Irvin 1
PMCID: PMC330058  PMID: 7527430

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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