The interaction between salmeterol and β2‐adrenoceptor agonists with higher efficacy on guinea‐pig trachea and human bronchus in vitro

Abstract

In guinea‐pig tracheal preparations precontracted with 1 μmol 1⁻¹ carbachol, formoterol, procaterol, fenoterol, salmefamol, salbutamol and terbutaline (in that order of potency) caused a concentration‐dependent and almost complete, relaxation. However, under these conditions, the maximum relaxation by salmeterol was approximately 30% of the maximum attainable relaxation. We have therefore explored the ability of salmeterol to inhibit the relaxant response to β₂‐adrenoceptor agonists of different chemical structure and relatively higher efficacy in smooth muscle preparations from guinea‐pig trachea and human bronchus. With 1 μmol 1⁻¹ salmeterol in the organ bath, the concentration‐effect curves for the other agonists were shifted to the right in a variable way by 1.8‐2.8 log units, fenoterol and salbutamol being the extremes. When 20 μmol 1⁻¹ sulfonterol, another low efficacy β₂‐adrenoceptor agonist, was substituted for salmeterol, the difference in the magnitude of the rightward shift between fenoterol and salbutamol was eliminated. In the human bronchus, formoterol and terbutaline had a higher apparent efficacy than salmeterol. With 1 μmol 1⁻¹ salmeterol in the organ bath, the concentration‐effect curve for formoterol was shifted 2.7 log units to the right. Salmeterol inhibits, competitively, relaxant responses to β₂‐adrenoceptor agonists with higher efficacy. The degree of inhibition seems to be dependent on the agonist used. This contrasts with results obtained with sulfonterol and suggests that salmeterol interacts with the β₂‐adrenoceptor in a complex way.