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

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.