NEUROKININ A-LI RELEASE AFTER ANTIGEN CHALLENGE IN GUINEA-PIG BRONCHIAL TUBES - INFLUENCE OF HISTAMINE AND BRADYKININ

1. Our aim was to determine if antigen challenge stimulates sensory ne rves and provokes the release of tachykinins. The involvement of hista mine and bradykinin was studied by using specific receptor antagonists . Capsaicin-induced responses were also examined. Experiments were per formed in vitro on tracheal and bronchial preparations from ovalbumin- sensitized guinea-pigs. 2. Characterization of ovalbumin-induced contr action, with regard to histamine and bradykinin, was carried out on ai rway ring preparations in the presence of phosphoramidon. The histamin e H-1 receptor antagonist pyrilamine reduced allergen-induced bronchia l contractions by about 30%, whereas the bradykinin B-2 receptor antag onist icatibant (Hoe 140) did not significantly affect the response. C ombined treatment with pyrilamine (1 mu M) and icatibant (0.1 mu M) re duced the contractions by about 80%, indicating a synergistic inhibito ry action. Tracheal preparations were not significantly affected by tr eatments, neither were capsaicin-induced contractions. 3. To study the outflow of tachykinins, we used a perfused bronchial-tube preparation , allowing simultaneous measurement of smooth muscle tension and media tor release. Neurokinin A-like immunoreactivity (NKA-LI) and substance P-like immunoreactivity (SP-LI) were determined by radioimmunoassay. 4. The results of the perfusion study showed an increased outflow of N KA-LI into the perfusate in response to ovalbumin (127% of basal) chal lenge. SP-LI determined in some of the samples showed a much lower amo unt (40 to 70 times lower) of SP-LI than NKA-LI. Treatment with icatib ant and pyrilamine, separately and in combination, significantly reduc ed the ovalbumin-induced NKA-LI outflow by 38%, 26% and 22%, respectiv ely. 5. Capsaicin-induced outflow (124% of basal) was not significantl y affected by treatments (icatibant 121%, pyrilamine 107% and combined treatment 111% of basal). However, when pyrilamine was present the in creased outflow was not statistically significant. 6. In conclusion, w e found that allergen provocation of guinea-pig bronchi caused an incr eased outflow of NKA-LI that was reduced by treatment with both pyrila mine and icatibant. These findings demonstrate that the allergen-induc ed release of histamine and bradykinin stimulate sensory nerves and th ereby increase outflow of tachykinins that contribute to the allergic reaction.