Zhu S J, Hatcher L I, Brown J C, Whittle S M, Toews M L
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Recept Signal Transduct. 1996;6(3-4):131-40.
The effects of hypertonic sucrose and of intracellular potassium depletion on the intact-cell-binding properties of beta (beta AR) and alpha 1 (alpha 1AR) adrenergic receptors of DDT1 MF-2 hamster smooth muscle cells were investigated. These treatments are known to block clathrin assembly into coated pits, an early step in the pathway of receptor endocytosis. Conducting intact-cell-binding assays in the presence of 0.4 M sucrose markedly decreased the fraction of both beta ARs and alpha 1ARs converted during the assay to a form exhibiting low apparent affinity for agonists. Intracellular potassium depletion also decreased the fraction of both beta ARs and alpha 1ARs converted to this low-affinity form. In contrast the intact-cell-binding properties of antagonists were unaltered by these treatments. These results suggest a role for receptor internalization in conversion of both beta ARs and alpha 1ARs to their low-affinity forms. A model is proposed in which either an initial agonist-induced receptor sequestration within the plasma membrane or the subsequent endocytosis of receptors into intracellular vesicles allows conversion of these receptors to the form exhibiting low affinity for agonists in binding assays with intact cells.
