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Keywords:

  • Airway smooth muscle;
  • bradykinin;
  • B2 receptor;
  • Na+-H+ exchanger;
  • Na+-K+ pump;
  • ouabain;
  • rubidium-86;
  • trachea
  • The effect of bradykinin on the Na+-K+ pump of airway smooth muscle was investigated by measuring ouabain-sensitive 86Rb+ uptake in cultured guinea-pig tracheal smooth muscle cells.

  • Bradykinin induced a concentration-dependent increase in ouabain-sensitive 86Rb+ uptake, with an EC50 of 3 nM (pD2=8.50±0.10). Stimulation was not affected by indomethacin (1 μM) suggesting that it is not mediated by cycloxygenase products of arachidonic acid.

  • The B1 receptor agonists Lys-des-Arg9-bradykinin and des-Arg9-bradykinin had no effect on ouabain-sensitive 86Rb+ uptake. In contrast, the B1 and B2 receptor agonist Lys-bradykinin induced a concentration-dependent increase in ouabain-sensitive 86Rb+ uptake with an EC50 of 6 nM (pD2=8.21±0.20).

  • The B1 receptor antagonist des-Arg10-HOE 140 (1 μM) had no effect on bradykinin-stimulated ouabain-sensitive 86Rb+ uptake. The B2 receptor antagonists HOE 140 and WIN 64338 antagonized bradykinin-stimulated ouabain-sensitive 86Rb+ uptake with pKB values (−log M) of 8.20±0.08 and 8.11±0.20 respectively.

  • Reducing extracellular Na+ from 146 mM to 11 mM caused a 53.5% decrease in basal ouabain-sensitive 86Rb+ uptake and abolished bradykinin-induced uptake. Two inhibitors of the Na+-H+ exchanger, methylisobutyl-amiloride (MIA; 1–100 μM) and ethylisopropyl-amiloride (EIPA; 0.1–10 μM), inhibited bradykinin-stimulated ouabain-sensitive 86Rb+ uptake without affecting basal uptake.

  • These results suggest that bradykinin increases Na+-K+ pump activity of guinea-pig tracheal smooth muscle via stimulation of B2 receptors and activation of the Na+-H+ exchanger.

British Journal of Pharmacology (2001) 133, 1339–1345; doi:10.1038/sj.bjp.0704198