Article date: January 1995
By: A. Silva, Y. Amrani, A. Trifilieff, Y. Landry, in Volume 114, Issue 1, pages 103-108
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.
In the resting tracheal preparation, bradykinin (0.1 nm − 30 μm induced a concentration‐related contractile response (pD2 = 8.8 ± 0.3). The maximal tension (1056 ± 321 mg) was observed at 0.3 μm bradykinin. In contrast, when tracheal preparations were pre‐contracted with histamine (30 μm leading to a half‐maximum response), a concentration‐related relaxation was observed with bradykinin. At the highest concentration of bradykinin used (3 μm), 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 μm). In concentration‐response curves, melittin (10 nm − 1 μm), a direct activator of phospholipase A2, mimicked both effects of bradykinin. The highest concentration of melittin used (1 μm), 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 μm) and AA861 (1 μm), a 5‐lipoxygenase inhibitor.
[Des Arg9]‐bradykinin (1 nm‐3 μm), 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). Hoe 140 (0.1 μm to 0.6 μm) behaved as a non‐competitive antagonist with an apparent pA2 = 7.2 ± 0.4, whereas NPC 17761 (0.3 to 1 μm) competitively antagonized bradykinin‐induced relaxation with a pKB = 7.3 ± 0.2. The Schild regression slope did not differ from unity, 0.96 ± 0.20, P < 0.05.
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.
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.
In the resting tracheal preparation, bradykinin (0.1 nm − 30 μm induced a concentration‐related contractile response (pD2 = 8.8 ± 0.3). The maximal tension (1056 ± 321 mg) was observed at 0.3 μm bradykinin. In contrast, when tracheal preparations were pre‐contracted with histamine (30 μm leading to a half‐maximum response), a concentration‐related relaxation was observed with bradykinin. At the highest concentration of bradykinin used (3 μm), 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 μm). In concentration‐response curves, melittin (10 nm − 1 μm), a direct activator of phospholipase A2, mimicked both effects of bradykinin. The highest concentration of melittin used (1 μm), 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 μm) and AA861 (1 μm), a 5‐lipoxygenase inhibitor.
[Des Arg9]‐bradykinin (1 nm‐3 μm), 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). Hoe 140 (0.1 μm to 0.6 μm) behaved as a non‐competitive antagonist with an apparent pA2 = 7.2 ± 0.4, whereas NPC 17761 (0.3 to 1 μm) competitively antagonized bradykinin‐induced relaxation with a pKB = 7.3 ± 0.2. The Schild regression slope did not differ from unity, 0.96 ± 0.20, P < 0.05.
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.
DOI: 10.1111/j.1476-5381.1995.tb14912.x
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