Studies of the stimulation and desensitization of beta adrenergic receptors in the human lymphocyte

Lymphocytes, were employed in radioligand binding studies of beta-adrenergic receptor density and affinity for agonists and in studies of isoproterenol stimulated adenylate cyclase activity. Studies of isoproterenol stimulation of adenylate cyclase activity demonstrated a role for extracellular calcium ions but not for extracellular magnesium ions in this process. Responses were diminished by chelation or by removal of extracellular calcium, as well as by lanthanum ion which competes with calcium for membrane binding sites. Initial studies using 3H-dihydroalprenolol (3H-DHA) indicated that 40% of cell surface beta receptors are lost during exposure of lymphocytes to isoproterenol and that the remaining receptors have a reduced affinity for beta agonists. Results from studies with 125iodocyanopindolol (125ICYP) are consistent with the view that beta receptors lost from the cell surface during isoproterenol treatment are present in a internal compartment of the cell. In mild asthmatic patients receiving a three week regimen of oral terbutaline a 40% reduction in the total receptor population was observed, suggesting that degradation of internalized receptors had occurred