Heterogeneity of adenylate cyclase-coupled β-adrenergic receptors

Abstract

The pharmacological characteristics of adenylate cyclase-coupled β-adrenergic receptors were determined by examining potency series of β-adrenergic agonists and antagonists on adenylate cyclase activity in membranes from six tissues: canine myocardium, diaphragmatic skeletal muscle, liver, lung, rat paraovarian fat and frog erythrocytes. Agonists were: isoproterenol, epinephrine, norepinephrine, soterenol and dobutamine. Antagonists were: d, l-propranolol, dichlorisoproterenol, practolol (a selective β 1 antagonist) and butoxamine (a selective β 2 antagonist). Catecholamine stimulation of adenylate cyclase ranged from 1.7-fold in lung membranes to 9.1-fold in frog erythrocyte membranes. Isoproterenol was the most potent agonist and propranolol the most potent antagonist in all tissues. Norepinephrine was a potent agonist in cardiac and adipose membranes ( 1 3 – 1 5 isoproterenol) but was much weaker in the other tissues ( 1 50 – 1 1000 isoproterenol). Soterenol was very weak in cardiac membranes but equipotent with norepinephrine and epinephrine in adipose membranes. Soterenol was more potent than norepinephrine in muscle, liver, lung and erythrocyte membranes. Practolol was a more potent antagonist than butoxamine in heart and adipose membranes, but the reverse was true in the other tissues. The potency ratio of practolol to butoxamine was 10 in fat, 5.8 in heart, 0.16 in muscle, 0.15 in liver and 0.07 in erythrocyte membranes. These results correlate reasonably well with previously determined results in more intact preparations. They suggest that adenylate cyclase-coupled β-adrenergic receptors reflect the specificity of physiological β-adrenergic receptors. The receptors in cardiac and adipose membranes appear to be β 1- and those in muscle, liver, lung and erythrocyte β 2-adrenergic receptors. The data also indicate heterogeneity of the receptors within each subclass (e.g. potency of soterenol in adipose vs cardiac membranes).