Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes

• Published in: British journal of pharmacology 1988-11, Vol.95 (3), p.723-734
• Main Authors: Bond, Richard A., Clarke, David E.
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Ileum - drug effects; Intestine. Mesentery; Male; Muscle Contraction - drug effects; Receptors, Adrenergic - drug effects; Vertebrates: digestive system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb11698.x

1 Experiments were done to characterize a putative adrenoceptor which functions to inhibit longitudinal muscle tension development in the guinea‐pig ileum. Several phenylethylamine based agonists were investigated: BRL 37344, (−)‐isoprenaline, (+)‐isoprenaline, noradrenaline, adrenaline, and fenoterol. Propranolol and nadolol were tested as antagonists. Agonist‐induced inhibition of the contractile response to histamine was measured under equilibrium conditions with α‐adrenoceptors and muscarinic cholinoceptors inhibited. 2 Inhibitory responses were obtained to (−)‐isoprenaline and BRL 37344 that were resistant to β‐adrenoceptor blockade with propranolol (5 μm) and nadolol (10μm). These resistant responses were antagonized by much higher concentrations of nadolol (30 to 1000 μm) yielding apparent pA2 values for nadolol of 4.31 with (−)‐isoprenaline as the agonist, and 4.68 with BRL 37344 as the agonist. Similar apparent pA2 values for nadolol at the putative adrenoceptor were obtained with noradrenaline (4.79), adrenaline (4.68), and fenoterol (4.38). 3 The order and relative potency of agonists at the putative adrenoceptor was: BRL 37344 (20) > (−)‐isoprenaline (8) > noradrenaline (1) > adrenaline (0.5) > fenoterol (0.35) > (H‐)‐isoprenaline (0.27). 4 The resistance to blockade by propranolol (5 μm), the low affinity of nadolol, and the order and relative potency of agonists, suggest the presence of an adrenoceptor with distinct pharmacological characteristics from currently defined α‐ and β‐adrenoceptors.