Involvement of enhanced neurokinin NK 3 receptor expression in the severe asthma guinea pig model

Abstract

In this study, we investigated the involvement of neurokinin NK 3 receptors in a severe asthma model prepared by administering ovalbumin via inhalation three times to systemically sensitized guinea pigs. [ 3H]senktide, a neurokinin NK 3 receptor ligand, showed significant specific binding to the lungs from the model animals, but not to those from negative control animals. The airway responsiveness to intravenous neurokinin B, a neurokinin NK 3 receptor agonist, was increased in the model, indicating an increase in functional NK 3 receptors. Furthermore, SB 223956 ((−)-3-methoxy-2-phenyl- N-[(1 S)-phenylpropyl]quinoline-4-carboxamide), a selective neurokinin NK 3 receptor antagonist, significantly inhibited the ovalbumin-induced airway hyperresponsiveness to inhaled methacholine, but it did not show significant effects on the ovalbumin-induced airway narrowing and eosinophil accumulation. These results suggest that the expressed neurokinin NK 3 receptors in the severe asthma model are involved in the development of airway hyperresponsiveness.