1 The aim of this study was to determine the receptor type and involvement of arachidonic acid metabolites in bradykinin-induced relaxation of the guinea-pig isolated trachea. 2 In the resting tracheal preparation, bradykinin (0.1 nM-30 LM induced a concentration-related contractile response (pD2 = 8.8 ± 0.3). The maximal tension (1056 ± 321 mg) was observed at 0.3 4M bradykinin. In contrast, when tracheal preparations were pre-contracted with histamine (30 LM leading to a half-maximum response), a concentration-related relaxation was observed with bradykinin. At the highest concentration of bradykinin used (3 LM), a reversal of 63 ± 13% of the contractile response to histamine was observed. Both effects of bradykinin were inhibited by the cyclo-oxygenase inhibitor, indomethacin (1I M). In concentration-response curves, melittin (1O nM-1 jM), a direct activator of phospholipase A2, mimicked both effects of bradykinin. The highest concentration of melittin used (1 tM), induced a tension of 813 ± 120 mg and led to the reversal of 41 ± 8% of the contractile response to histamine. The contractile effect of melittin was inhibited in the presence of both indomethacin (1 jM) and AA861 (1 jM), a 5-lipoxygenase inhibitor. . 4 These data demonstrate that bradykinin-induced relaxation of guinea-pig trachea occurs via the activation of bradykinin B2-receptors. The stimulation of B2-bradykinin receptors induces the activation of the cyclo-oxygenase pathway, leading either to contraction or relaxation depending on the tone of the trachea.

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