Hydrocortisone-induced reversal of beta-adrenergic receptor uncoupling.

Prolonged exposure to adrenal-steroid hormones or adrenergic agonists results in opposing physiologic effects on beta-adrenergic receptors. These physiologic events have biochemical correlates that can be evaluated in the laboratory setting. The ability of hydrocortisone in vitro to reverse prior uncoupling of the receptor induced by terbutaline in vivo was examined. Healthy human volunteers received terbutaline sulfate, 2.5 mg orally every 8 h for 3 days, for a total of 9 doses. Neutrophils obtained from these volunteers were then incubated for 3 h in vitro in the presence of either hydrocortisone or saline placebo. Two types of receptor alterations were observed. Receptor density was reduced by 28% in terbutaline-treated subjects as compared with that in untreated control subjects (p less than 0.016). The receptors also appeared to be relatively uncoupled. This was assessed by examining the ability of the agonist isoproterenol to stabilize a high affinity form of the receptor detected by computer modeling of competition curves for [125I]cyanopindolol binding. The reduction in receptor density was not affected by incubation in hydrocortisone. The ability of isoproterenol to stabilize the high affinity form of the receptor in cells incubated with hydrocortisone was statistically indistinguishable from that of the control state. We conclude that hydrocortisone can reverse prior agonist-induced uncoupling in vitro without affecting prior homologous down regulation.