Abstract
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 microM induced a concentration-related contractile response (pD2 = 8.8 +/- 0.3). The maximal tension (1056 +/- 321 mg) was observed at 0.3 microM bradykinin. In contrast, when tracheal preparations were pre-contracted with histamine (30 microM leading to a half-maximum response), a concentration-related relaxation was observed with bradykinin. At the highest concentration of bradykinin used (3 microM), 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 (1 microM). In concentration-response curves, melittin (10 nM-1 microM), a direct activator of phospholipase A2, mimicked both effects of bradykinin. The highest concentration of melittin used (1 microM), 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 microM) and AA861 (1 microM), a 5-lipoxygenase inhibitor. 3. [Des Arg9]-bradykinin (1 nM-3 microM), a B1-receptor agonist, was unable to relax precontracted guinea-pig tracheal preparations. The relaxation induced by bradykinin was antagonized by the B2 receptor antagonists, Hoe 140 (D-Arg0[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) and NPC 17761 (D-Arg0[Hyp3,D-HypE(trans-thiophenyl)7,Oic8]bradykinin ).(ABSTRACT TRUNCATED AT 250 WORDS)
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