A response to isoprenaline unrelated to α‐and β‐adrenoceptor agonism

Abstract

1 The hypothesis that β-adrenoceptor agonism might explain a reported lack of competitive antagonism between α₂-adrenoceptor antagonists and agonists of the phenylethylamine class was tested in the electrically field stimulated ileum of the guinea-pig. The β-adrenoceptor agonist, isoprenaline, was used as the phenylethylamine and inhibition of ‘twitch’ response evoked by cholinergic stimulation was measured. 2 In the presence of idazoxan (3 μm), to block inhibitory α₂-adrenoceptors, propranolol (0.1 to 5.0 μm) failed to act competitively toward isoprenaline. Isoprenaline responses totally resistant to inhibition by propranolol were obtained. 3 As inhibitory α₁-adrenoceptors are absent from guinea-pig ileum, a recognition site distinct from the currently defined α-and β-adrenoceptors is postulated. Agonism by phenylethylamine based agonists at this site may explain their inability to act competitively with α-and β-adrenoceptor antagonists.