Effects of β‐adrenoceptor agonists in human bronchial smooth muscle

Abstract

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. 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. Relaxant responses to salmeterol were fully reversed by the selective β2‐adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of β2‐adrenoceptors. 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. 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. 1993 British Pharmacological Society