Biphasic Adrenergic Modulation of β-Adrenergic Receptors in Man: AGONIST-INDUCED EARLY INCREMENT AND LATE DECREMENT IN β-ADRENERGIC RECEPTOR NUMBER

: beta-Adrenergic receptors in mononuclear leukocyte preparations were assessed with (-)[(3)H]-dihydroalprenolol binding studies during the infusion of adrenergic agonists into normal human subjects. During the infusion of isoproterenol into seven subjects, mean (+/-SE) (-)[(3)H]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 (-)[(3)H]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 (-)[(3)H]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 beta-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 beta-adrenergic receptor number on circulating cells is paralleled by increments in extra-vascular beta-adrenergic receptor sensitivity.