A response to isoprenaline unrelated to alpha- and beta-adrenoceptor agonism.
The hypothesis that beta-adrenoceptor agonism might explain a reported lack of competitive antagonism between alpha 2-adrenoceptor antagonists and agonists of the phenylethylamine class was tested in the electrically field stimulated ileum of the guinea-pig. The beta-adrenoceptor agonist, isoprenaline, was used as the phenylethylamine and inhibition of 'twitch' response evoked by cholinergic stimulation was measured. In the presence of idazoxan (3 microM), to block inhibitory alpha 2-adrenoceptors, propranolol (0.1 to 5.0 microM) failed to act competitively toward isoprenaline. Isoprenaline responses totally resistant to inhibition by propranolol were obtained. As inhibitory alpha 1-adrenoceptors are absent from guinea-pig ileum, a recognition site distinct from the currently defined alpha- and beta-adrenoceptors is postulated. Agonism by phenylethylamine based agonists at this site may explain their inability to act competitively with alpha- and beta-adrenoceptor antagonists.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D012110:Reserpine; D007545:Isoproterenol; D009638:Norepinephrine