Involvement of kinins and tachykinins in the development of nasal hyperresponsiveness in a guinea pig pollinosis model

Abstract

Although it has been suggested that kinins and tachykinins may be involved in the pathogenesis of allergic rhinitis, inhibitors of these mediators have not yet to be developed for use as therapeutic drugs. Therefore, this study examined whether kinins and tachykinins are involved in the induction of nasal symptoms in a guinea pig pollinosis model.Sensitized guinea pigs were challenged by forced inhalation of pollen once a week. Sneezing and nasal blockage were observed after pollen challenges. Nasal hyperresponsiveness to an intranasal application of leukotriene (LT) D4 was assessed 2 days after an antigen challenge.Neither bradykinin receptor (B1 and B2) antagonists nor tachykinin receptor (NK1 and NK2) antagonists inhibited sneezing and nasal blockage. In contrast, these antagonists significantly suppressed the development of nasal hyperresponsiveness. An especially strong inhibition was noted for the B2 receptor and the NK2 receptor antagonists. Furthermore, exogenous intranasal instillation of kinins (bradykinin and des-Arg10-kallidin) and tachykinins (neurokinin A and substance P) produced nasal hyperresponsiveness that was similar to the antigen-antibody reaction. On the other hand, immediately after a pollen challenge, an increase was noted in the amount of bradykinin in the nasal cavity lavage fluid, followed by elevation of tachykinin levels.These results indicate that kinins and tachykinins mediate the development of nasal hyperresponsiveness by preferentially activating B2 and NK2 receptors. Therefore, these receptor antagonists may prove effective in the treatment of allergic rhinitis.