Effects of β‐adrenoceptor agonists in human bronchial smooth muscle

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Abstract
1 We have investigated the potency and duration of action of isoprenaline and a range of β-adrenoceptor agonists as relaxants of inherent tone in human superfused, isolated bronchial smooth muscle, a tissue reported to contain a homogeneous population of β2-adrenoceptors. 2 All of the β-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 ≥-salmeterol ≥ clenbuterol > fenoterol = isoprenaline > terbutaline ≥ salbutamol > quinprenaline. 3 Relaxant responses to salmeterol were fully reversed by the selective β2-adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of β2-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 β2-adrenoceptor agonists. Most agonists were short-acting, having Rt50 values less than 13 min. Quinprenaline was of moderate duration, with an Rt50 value of ≥ 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 β-adrenoceptor agonists on airways smooth muscle.