Cell metabolism affects the density of β-adrenergic receptors in intact rat reticulocytes

Abstract

Membrane receptors mediating the cellular effects of fi-adrenergic compounds can be identified by studying stereoselective binding of radioactively labelled specific ligands. Such P-adrenoceptors have been identified in a large variety of different cells and tissues, among them nucleated avian red cells and mamma~an reticulocytes [ I-41. Most authors have studied the properties of @-adrenoceptors in isolated membrane preparations rather than in intact cells in order to reduce possible interference from nonspecific cellular uptake and binding processes. However, the few reports on P-adrenergic binding in intact cells [5-S] have tended to confirm the results obtained with membrane particles. We have used intact rat reticulocytes to study possible regulatory effects of cell metabolism on &adrenoceptor binding. Stereospecific binding of the /3-adrenergic antagonist (-) L3H] d~ydroalprenolol (DHAP) and its competitive displacement of unlabelled fl-adrenergic agonists and antagonists was measured under conditions which cannot be mimicked in membrane fragments. We report that the number of fl-adrenoceptors decreases considerably during metabolic inhibition. This finding ch~lenges the assumption that regulatory changes in P-receptor densities of intact cells are faithfully reflected in the data derived from binding studies in fragmented membrane preparations.