β-Adrenergic receptors in mononuclear leukocyte preparations were assessed with (−)[3H]-dihydroalprenolol binding studies during the infusion of adrenergic agonists into normal human subjects. During the infusion of isoproterenol into seven subjects, mean (±SE) (−)[3H]dihydroalprenolol binding increased from 25±3 fmol/mg protein to 47±8 fmol/mg protein (P < 0.02) at 0.5 h and 40±3 fmol/mg protein (P < 0.01) at 1 h and decreased to 12±1 fmol/mg protein (P < 0.01) at 4-6 h. During the infusion of epinephrine into three subjects, mean (−)[3H]dihydroalprenolol binding increased from 32±3 to 63±3 fmol/mg protein (P < 0.01) at 0.5-1 h. By Scatchard plot analysis, these changes were attributable to changes in the number of available binding sites rather than changes in binding affinity. The observed changes in the number of (−)[3H]dihydroalprenolol binding sites were not paralleled by changes in total mononuclear cell counts or in T lymphocyte, B lymphocyte, and monocyte distributions. Thus, we conclude that adrenergic agonists modulate the number of available β-adrenergic receptors on circulating mononuclear cells in a biphasic manner, with an early increment and a late decrement, in man. Further, the finding that the increase in pulse rate in response to a “pulse” infusion of isoproterenol was significantly greater after 0.5-1 h of agonist infusion suggests that the observed early agonist-induced increment in β-adrenergic receptor number on circulating cells is paralleled by increments in extra-vascular β-adrenergic receptor sensitivity.
Jack F. Tohmeh, Philip E. Cryer
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