Involvement of enhanced neurokinin NK3 receptor expression in the severe asthma guinea pig model

In this study, we investigated the involvement of neurokinin NK3 receptors in a severe asthma model prepared by administering ovalbumin via inhalation three times to systemically sensitized guinea pigs. [H-3]senktide, a neurokinin NK3 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 NK3 receptor agonist, was increased in the model, indicating an increase in functional NK3 receptors. Furthermore, SB 223956 ((-)-3-methoxy-2-phenyl-N-[(1S)-phenylpropyl]quinoline-4-carboxamide), a selective neurokinin NK3 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 NK3 receptors in the severe asthma model are involved in the development of airway hyperresponsiveness. (C) 2004 Elsevier B.V. All rights reserved.