In Vivo Regulation ofβ-Adrenergic Receptors onHuman Mononuclear Leukocytes: Assessment of Receptor Number, Location, and Function after Posture Change, Exercise, and Isoproterenol Infusion*
We studied the regulation ofβ-adrenergic receptors in human mononuclear leukocytes (MNL). Total receptor number was determined as specific binding at 4 C of[3H] dihydroalprenolol or[125I]iodopindolol, and redistributed receptors were defined asthose binding sites to which the hydrophilic antagonist CGP-12177 didnot have access. Receptor function was assessed as cAMP accumulation stimulated by isoprotere-nol. In in vitro experiments, high concentrations of isoproterenol desensitized receptor function and promoted redistribution of about 80% ofthe receptors away from the cell surface. However, three in vivo protocols (upright posture for 3 h, moderate exercise, and infusion of isoproterenol for30min) redistributed few β-adrenergic receptors on MNL.The30-min isoproterenol infusion did not alter later cAMP accumulation, but posture change and exercise increased isoproterenol-stimulated cAMP accumulation in intact MNL. Infusion of isoproterenol for min redistributed 9 ± 2%(±SEM) ofthe receptors and decreased isoproterenol-stimulated cAMP accumulation by19 ± 6%. Iso proterenol-stimulated adenylate cyclase activity in membranes isolated from MNL previously was found to be decreased with upright posture, and weconfirmed these findings in assays that did not include exogenous GTP, but instead relied upon guanine nucleotides retained in the membrane preparation. However, when excess GTP was included, isoproterenol-stimulated ade-nylatecyclase activity in MNL membranes was notalteredby posture change. We conclude that substantial receptor redistribution of β-receptors on MNLdoes notreadily occur in physiological situations.