Agonist-Induced Redistribution of 0-Adrenergic Receptors on Intact Human Mononuclear Leukocyte Redistributed Receptors Are Nonfunctional*

Incubation of human mononuclear leukocytes (MLN) with isoproterenol rapidly desensitizes β-adrenegic receptors, i.e. isoproterenol-stimulated cAMP accumulation decreases. This desensitization is accompanied by a redistribution of the receptor into a cellular environment to which hydrophilic compounds have limited access. We found that the total number of β-receptors [defined as binding of [3H]dihydroalprenolol (DHA) inhibited by 1 pM propranolol] was unchanged in the desensitized MNL. In control MNL, virtually all DHA binding was inhibited by 1 μM CGP-12177, suggesting that all of these receptors are on the cell surface, whereas in desensitized cells, only 33 ± 2% (mean ± SEM) of the DHA binding was inhibited by CGP-12177. We quantitated the sequestered receptors by subtracting the number of surface receptors from the total number of receptors. The sequestered receptors were homogeneous, with an affinity for DHA identical to that of surface receptors (Kd, 0.66 ± 0.12 vs. 0.62 ± 0.08 nM). The time courses ...