S. Houjou et al., ALLERGIC RESPONSES REDUCE THE RELAXANT EFFECT OF BETA-AGONISTS BUT NOT POTASSIUM CHANNEL OPENERS IN GUINEA-PIG ISOLATED TRACHEA, The European respiratory journal, 9(10), 1996, pp. 2050-2056
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.