Effects of beta-adrenoceptor agonists in human bronchial smooth muscle.
1. We have investigated the potency and duration of action of isoprenaline and a range of beta-adrenoceptor agonists as relaxants of inherent tone in human superfused, isolated bronchial smooth muscle, a tissue reported to contain a homogeneous population of beta 2-adrenoceptors. 2. All of the beta-adrenoceptor agonists caused concentration-related inhibition of inherent tone, with isoprenaline having an EC50 of 27 nM. The rank order of agonist potency was: formoterol > or = -salmeterol > or = clenbuterol > fenoterol = isoprenaline > terbutaline > or = salbutamol > quinprenaline. 3. Relaxant responses to salmeterol were fully reversed by the selective beta 2-adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of beta 2-adrenoceptors. 4. Rt50, i.e. the time taken for 50% recovery from the effects of an EC50 concentration of agonist, differed considerably between the different beta 2-adrenoceptor agonists. Most agonists were short-acting, having Rt50 values less than 13 min. Quinprenaline was of moderate duration, with an Rt50 value of > or = 20 min. In contrast, salmeterol was extremely long-acting, with no sign of recovery within 4 h. 5. Estimates of relative potency and duration of action were similar to those previously determined for these agonists in the guinea-pig isolated trachea. These results suggest, therefore, that guinea-pig trachea is a suitable alternative to human bronchus for the evaluation of the actions of beta-adrenoceptor agonists on airways smooth muscle.
Nials
A T
AT
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd., Ware, Herts.
Coleman
R A
RA
Johnson
M
M
Magnussen
H
H
Rabe
K F
KF
Vardey
C J
CJ
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013997:Time Factors
D000318:Adrenergic beta-Agonists