Inhibitory effects of capsazepine and SR 48968 on citric acid-induced bronchoconstriction in guinea-pigs

We have examined the effects of capsazepine, a selective capsaicin antagonist, and SR 48968, a selective NK2 receptor antagonist, on citric acid inhalation-induced bronchoconstriction in guinea-pigs. Simultaneous inhalation of capsazepine (10 microM) significantly inhibited (by 85%) the bronchoconstriction induced by inhaled citric acid (0.4 M) but not that induced by histamine (2 mM). In capsaicin-pretreated (50 mg/kg s.c. 3 weeks earlier) guinea-pigs, citric acid failed to cause any bronchoconstriction, while the effect of histamine was uninfluenced. Furthermore, citric acid inhalation-induced bronchoconstriction was also markedly inhibited (by 65%) after pretreatment with SR 48968 (0.3 mg/kg i.v.). SR 48968 blocked the bronchoconstriction but not the hypotension evoked by neurokinin A. Therefore, these results suggest that inhalation of a low-pH solution such as citric acid can stimulate sensory neurons through a mechanism similar to that for capsaicin with regard to sensitivity to capsazepine. Tachykinins such as neurokinin A are then locally released from the terminals of sensory nerves and cause bronchoconstriction, mainly by NK2 receptor mechanisms.