Extent of salmeterol-mediated reassertion of relaxation in guinea-pig trachea pretreated with aliphatic side chain structural analogues

Abstract

1 Salmeterol is a potent, selective and long acting β2-adrenoceptor agonist. In vitro, salmeterol exerts 'reassertion' relaxation of airways smooth muscle. Reassertion relaxation refers, to the capacity of salmeterol to cause repeated functional antagonism of induced contraction when airway smooth muscle is intermittently exposed to, then washed free from, β-adrenoceptor antagonists such as sotalol. The mechanism(s) underlying reassertion relaxation are unknown but may relate to high affinity binding of the long aliphatic side chain of salmeterol to an accessory site, distinct from the agonist recognition site, in or near the β2-adrenoceptor (exosite binding hypothesis). 2 In order to test t..