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.
Nielsen-Kudsk
J E
JE
Institute of Pharmacology, University of Aarhus, Denmark.
Bang
L
L
Brønsgaard
A M
AM
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors*; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009125:Muscle Relaxants, Central / Q000037:antagonists & inhibitors*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D020110:Pinacidil; D011758:Pyrroles / Q000037:antagonists & inhibitors*; D013726:Terbutaline / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D009125:Muscle Relaxants, Central; D011758:Pyrroles; D019806:Cromakalim; D020110:Pinacidil; D006632:Histamine; D013806:Theophylline; D014700:Verapamil; D013726:Terbutaline; D005905:Glyburide