Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines

Abstract

β-Adrenergic receptors on human mononuclear leukocytes were assessed using [125I]iodohydroxybenzylpindolol binding. Subjects were studied supine and after being ambulatory, a maneuver that increases plasma catecholamines approximately two-fold. β-Receptor affinity for agonists, measured by the competition of [125I]iodohydroxybenzylpindolol binding by (-)isoproterenol was significantly reduced with ambulation and this reduction was associated with a reduction in the proportion of β-receptors binding agonist with a high affinity from a mean (±SEM) of 42 ± 5 to 24 ± 2% (P < 0.01). In a parallel series, β-adrenergic-stimulated adenylate cyclase activity was also reduced with postural change from 4.6 ± 1.1 to 2.4 ± 0.6 pmol [32P]cAMP/min per mg protein (P < 0.05) after ambulation. Similar reductions in the proportion of receptors binding agonist with a high affinity were seen after infusion of norepinephrine. We conclude that the maneuver of ambulation reduces leukocyte β-receptor responsiveness and affinity for agonists, probably by the effect of increased plasma catecholamines mediating an uncoupling of the β-receptor-adenylate cyclase complex.