Analysis of the relaxant action of SDZ PCO 400 in airway smooth muscle from the ox and guinea-pig.
SDZ PCO 400 (30 nM-100 microM) suppressed the spontaneous tone of guinea-pig isolated trachealis. Glibenclamide (1-10 microM), phentolamine (100 microM), guanethidine (50 microM) and bretylium (50 microM) each antagonized SDZ PCO 400 without antagonizing isoprenaline or theophylline. Charybdotoxin (100 nM) failed to antagonize SDZ PCO 400 but antagonized theophylline. The relaxant action of SDZ PCO 400 was ablated when spasm was induced by a K(+)-rich (120 mM) medium. In bovine and guinea-pig trachea, SDZ PCO 400 (10 microM) suppressed spasm evoked by lower (less than 40 mM) but not higher (greater than 40 mM) concentrations of KCl. In guinea-pig trachea the relaxant action of SDZ PCO 400 was associated with suppression of electrical slow waves and with marked cellular hyperpolarisation. SDZ PCO 400 (0.5 and 10 microM) promoted the efflux of 86Rb+ from bovine trachealis, an effect inhibited by glibenclamide (1 microM). It is concluded that the tracheal relaxant action of SDZ PCO 400 is associated with the opening of a plasmalemmal K(+)-channel analogous to the ATP-sensitive K(+)-channel observed in insulin-secreting cells.
Small
R C
RC
Department of Physiological Sciences, University of Manchester, UK.
Berry
J L
JL
Foster
R W
RW
Blarer
S
S
Quast
U
U
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001949:Bretylium Compounds / Q000494:pharmacology; D002417:Cattle; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D012414:Rubidium Radioisotopes / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001578:Benzopyrans; D001949:Bretylium Compounds; D003517:Cyclopentanes; D010276:Parasympatholytics; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; C073091:SDZ PCO 400; C045166:bretylium; D005905:Glyburide; D006145:Guanethidine