Journal of Clinical Endocrinology & Metabolism, Vol 63, 847-853, Copyright © 1986 by Endocrine Society

ARTICLES

In vivo regulation of beta-adrenergic receptors on human mononuclear leukocytes: assessment of receptor number, location, and function after posture change, exercise, and isoproterenol infusion

A DeBlasi, AS Maisel, RD Feldman, MG Ziegler, M Fratelli, M DiLallo, DA Smith, CY Lai and HJ Motulsky

We studied the regulation of beta-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 as those binding sites to which the hydrophilic antagonist CGP-12177 did not have access. Receptor function was assessed as cAMP accumulation stimulated by isoproterenol. In in vitro experiments, high concentrations of isoproterenol desensitized receptor function and promoted redistribution of about 80% of the receptors away from the cell surface. However, three in vivo protocols (upright posture for 3 h, moderate exercise, and infusion of isoproterenol for 30 min) redistributed few beta-adrenergic receptors on MNL. The 30-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 120 min redistributed 9 +/- 2% (+/- SEM) of the receptors and decreased isoproterenol-stimulated cAMP accumulation by 19 +/- 6%. Isoproterenol- stimulated adenylate cyclase activity in membranes isolated from MNL previously was found to be decreased with upright posture, and we confirmed 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 adenylate cyclase activity in MNL membranes was not altered by posture change. We conclude that substantial receptor redistribution of beta-receptors on MNL does not readily occur in physiological situations.

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