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Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes
Author(s) -
Bond Richard A.,
Clarke David E.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11698.x
Subject(s) - nadolol , isoprenaline , fenoterol , agonist , propranolol , endocrinology , medicine , chemistry , atenolol , antagonist , potency , intrinsic activity , pharmacology , receptor , biology , stimulation , in vitro , biochemistry , blood pressure , asthma
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 μ m ) and nadolol (10μ m ). These resistant responses were antagonized by much higher concentrations of nadolol (30 to 1000 μ m ) yielding apparent pA 2 values for nadolol of 4.31 with (−)‐isoprenaline as the agonist, and 4.68 with BRL 37344 as the agonist. Similar apparent pA 2 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 μ m ), 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.