Glibenclamide blocks the relaxant action of pinacidil and cromakalim in airway smooth muscle.

Concentration-relaxation curves for pinacidil and cromakalim were obtained in isolated guinea-pig tracheas contracted by histamine. Pinacidil produced complete relaxation with an EC50 value of 2.8 microM. The antidiabetic sulfonylurea, glibenclamide (0.1, 1, 10 microM), caused concentration-dependent rightward shifts (3- to 16-fold) of the concentration-relaxation curve for pinacidil without changing the maximal relaxant response. Cromakalim produced 85% relaxation with an EC50 value of 1.1 microM. Glibenclamide (0.1 microM) displaced the concentration-relaxation curve to the right and at higher concentrations (1-10 microM) caused nearly complete suppression of the maximal relaxant response to cromakalim. Glibenclamide not only prevented the effects of pinacidil and cromakalim but also produced a concentration-dependent and complete reversal of submaximal relaxations produced by these drugs. Glibenclamide was a selective antagonist of the relaxation of airway smooth muscle induced by pinacidil and cromakalim. Concentration-relaxation curves for theophylline, terbutaline and verapamil were unaffected by glibenclamide.