Tracheal relaxation induced bypotassium channel opening drugs: itsantagonism byadrenergic neurone blocking agents

1 We havestudied theability ofsome adrenergic neurone blocking agentsto inhibit thetracheal relaxant actions ofisoprenaline, theophylline andthepotassium channel openers (KCOs)BRL 38227, pinacidil andRP 52891. 2 BRL38227, isoprenaline, pinacidil, RP 52891andtheophylline eachcaused concentration-dependent suppression ofthespontaneous toneofguinea-pig isolated trachealis. Themaximalrelaxant effects of isoprenaline andpinacidil were equal tothatoftheophylline. Incontrast, themaximaleffects ofBRL 38227andRP 52891 were approximately 85-95%ofthatoftheophylline. 3 Guanethidine (5-5001iM) didnotitself modifythespontaneoustoneofthetrachealis musclebut antagonized BRL 38227ina concentration-dependent manner. Guanethidine (50LM)alsoantagonized pinacidil andRP 52891. However, guanethidine didnotantagonize either isoprenaline or theophylline. 4 Bretylium (50LM)didnotitself modifythespontaneous toneofthetrachealis musclebutantagonized BRL 38227, pinacidil andRP 52891. Bretylium didnotantagonize either isoprenaline or theophylline. 5 Guanidine (50and500j1M) didnotitself modify thespontaneous toneofthetrachea andfailed to modifythetracheal relaxant activity bothofBRL 38227andtheophylline. 6 BRL 38227(1and10fiM) stimulated, ina concentration-dependent manner, theefflux of86Rb+from strips ofbovine trachealis muscle thathadbeenpre-loaded withtheradiotracer. Guanethidine (50iM), bretylium (50JiM) anddebrisoquine (50jiM) didnotthemselves modify theefflux of86Rb+frombovine trachealis buteachofthese agentsmarkedly inhibited thestimulant effect ofBRL 38227(10jiM) on 86Rb+efflux. 7 Itisconcluded thattheadrenergic neurone blocking agentsguanethidine andbretylium can inhibit thetracheal relaxant actions ofKCOssuch asBRL 38227, pinacidil andRP52891without antagonizing isoprenaline or theophylline. Theability oftheadrenergic neuroneblocking agentstoantagonize BRL 38227inpromoting 86Rb+efflux fromtrachealis muscle may suggestthattheadrenergic neurone blocking agentsacttopreventtheopening oftheplasmalemmal K+-channel thatisinvolved inthe tracheal relaxant actions oftheKCOs.