ALLERGIC RESPONSES REDUCE THE RELAXANT EFFECT OF BETA-AGONISTS BUT NOT POTASSIUM CHANNEL OPENERS IN GUINEA-PIG ISOLATED TRACHEA

This study was conducted to determine whether the relaxant effect of a denosine triphosphate (ATP)-sensitive potassium channel (KATP) openers on airway smooth muscle are reduced during the hyporesponsiveness of beta-adrenergic receptors. Isometric tension was measured and dose-res ponse curves were constructed for levcromakalim (a KATP opener), Y-267 63 (another KATP opener), isoprenaline and theophylline in guinea-pig isolated trachea that was challenged with ovalbumin or pretreated in v itro with either isoprenaline or the KATP openers. Antigen challenge i n vitro significantly reduced the potency but not the efficacy of isop renaline in tracheal strips from actively sensitized guinea-pigs. The concentration of drug that produced a half-maximum inhibition (IC50) w as 0.014+/-0.004 mu M in the challenge group versus 0.006+/-0.001 mu M in the control group (p<0.05; n=9), The IC50 of levcromakalim (1.73+/ -0.17 mu M; n=6) and of theophylline (110+/-3.1 mu M; n=6) were unaffe cted. Exposure to 4 mu M isoprenaline for 30 min evoked beta-adrenergi c hyporesponsiveness: the IC50 of isoprenaline rose significantly from 0.010+/-0.001 to 0.017+/-0.002 mu M (p<0.01; n=6). No effect was obse rved on the relaxant actions of levcromakalim and theophylline. In con trast, prior incubation with either levcromakalim or Y-26763 (300 mu M for 30 min) significantly reduced the subsequent potency and efficacy of levcromakalim, but did not alter the effects of isoprenaline and t heophylline. We conclude that the relaxant effect of the adenosine tri phosphate-sensitive potassium channel openers was independent of beta- adrenergic hyporesponsiveness in airway smooth muscle of guinea-pigs.