Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines.
beta-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. beta-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 beta-receptors binding agonist with a high affinity from a mean (+/- SEM) of 42 +/- 5 to 24 +/- 2% (P less than 0.01). In a parallel series, beta-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 less than 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 beta-receptor responsiveness and affinity for agonists, probably by the effect of increased plasma catecholamines mediating an uncoupling of the beta-receptor-adenylate cyclase complex.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D001667:Binding, Competitive; D004837:Epinephrine / Q000097:blood*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011187:Posture; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; C011878:iodohydroxybenzylpindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine