Antigen- and histamine H1 receptor-mediated relaxation of guinea pig isolated trachea

We have investigated the effect of challenge in vitro with specific antigen (ovalbumin) on actively sensitized guinea pig tracheal rings maximally precontracted with methacholine. Ovalbumin relaxed the trachea in a concentration-dependent fashion with a negative log ED50 value (g/ml) of 7.0 +/- 0.3. In 16 experiments, the maximum antigen-induced relaxation was 26 +/- 3% of complete relaxation induced by 10(-3) M papaverine (mean +/- S.E.M.). Antigen-induced relaxations were selectively antagonized by diphenhydramine. Similarly, histamine relaxed the precontracted tracheal smooth muscle with a negative log molar ED50 of about 4.5 and a maximum effect of 28 +/- 3% (mean +/- S.E.M., n = 20). Histamine-induced relaxations were antagonized by diphenhydramine and mepyramine but were unaffected by cimetidine, metiamide or burimamide. Dimaprit (10(-5)-10(-3) M) did not relax the precontracted trachea. Indomethacin significantly inhibited relaxation induced by both antigen and histamine. In contrast, phenidone or 5,8,11,14-eicosa-tetraynoic acid had no effect on relaxation but reversed the inhibition by indomethacin. Neither propranolol (10(-6) M) nor removing the tracheal epithelium inhibited histamine-induced relaxation. These results suggest that antigen-induced relaxation of guinea pig tracheal smooth muscle involves activation of histamine H1 receptors and can occur independently of arachidonic acid metabolism, beta-adrenoceptor activation or airway epithelium.