Bronchial responses to substance P after antigen challenge in the guinea-pig: in vivo and in vitro studies

E Boichot,P Braquet,N Frossard,C Carré,J M Mencia-Huerta,V Lagente,A Lockhart,G Le Gall

doi:10.1155/s0962935192000322

Abstract

The effect of antigen challenge on the airway responses to substance P and on the epithelial neutral endopeptidase (NEP) activity was investigated in aerosol sensitized guinea-pigs. In vivo, bronchial responses to aerosolized substance P were similar to the responses observed in antigen-challenged guinea-pigs and in the control groups. In contrast, when the guinea-pigs were pretreated with the NEP inhibitor, phosphoramidon, a significant increase in the airway responses to substance P was observed after antigen challenge in vivo. However, in vitro, the contractile responses of the tracheal smooth muscle to substance P were similar between groups of guinea-pigs, in respect to the presence or absence of the epithelium and/or phosphoramidon. Histological studies showed an accumulation of eosinophils in the tracheal submucosa after antigen challenge and intact epithelial cells. These results show that in vivo bronchial hyperresponsiveness to substance P after antigen challenge in the guinea-pig is not associated with increased responses of the smooth muscle to exogenous SP in vitro. In addition, the results with phosphoramidon suggest that loss of NEP activity cannot account for the in vivo bronchial hyperresponsiveness to substance P presently observed.

Highlights

Non-specific increase in airway responsiveness to bronchoconstrictor stimuli, namely bronchial hyperresponsiveness, is generally associated with airway inflammation in asthma
Effect of OA challenge on airway responses to acetylcholine and histamine: In vivo no significant difference in the initial pulmonary inflation pressure (PIP) was observed before stimulation with either acetylcholine, histamine or substance P between the different groups of guinea-pigs
The present study shows that antigen challenge in aerosol sensitized guinea-pigs induces in vivo airway hyperresponsiveness to substance P, acetylcholine and histamine, which is not associated with any modification of the smooth muscle response to these agents in vitro nor of its modulation by airway epithelium

Summary

Introduction

Non-specific increase in airway responsiveness to bronchoconstrictor stimuli, namely bronchial hyperresponsiveness, is generally associated with airway inflammation in asthma. Substance P and related neurokinins, mediators of the sensory pathway, may be locally released after stimulation of C fibre endings. These neuropeptides induce contraction of the airways in the guinea-pig and in human.2’3 They have pro-inflammatory effects in the airways4,s and may play a role in airway hyperresponsiveness. These neuropeptides may be degraded by neutral endopeptidase (NEP), an enzyme localized to airway epithelium. Bronchial hyperresponsiveness to substance P has been reported after viral infection or cigarette smoke. 11’12 Since the bronchoconstrictor responses to substance P were not increased after NEP blockade as compared to controls, hyperresponsiveness was attributed to an alteration in NEP activity. 1’2

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Conclusion