TY - JOUR T1 - A Desensitized State of the <em>Beta</em> Adrenergic Receptor Not Associated with High-Affinity Agonist Occupancy JF - Molecular Pharmacology JO - Mol Pharmacol SP - 376 LP - 380 VL - 14 IS - 2 AU - ROBERT J. LEFKOWITZ AU - DEBRA MULLIKIN AU - LEWIS T. WILLIAMS Y1 - 1978/03/01 UR - http://molpharm.aspetjournals.org/content/14/2/376.abstract N2 - Exposure of certain cells (e.g., frog erythrocytes) to beta adrenergic agonists leads to desensitization of the membrane-bound adenylate cyclase to further beta adrenergic stimulation, which is associated with a fall in the number of beta adrenergic receptor binding sites. To explain further the mechanism of this agonist-induced desensitization of adenylate cyclase-coupled beta adrenengic receptors, intact frog erythrocytes were "desensitized" by incubation with the radiolabeled beta adrenergic agonist [3H]hydroxybenzylisoproterenol. This incubation with agonist led to a "loss" of 33% of the (-)-[3H]dihydroalprenolol binding sites (beta adrenergic receptors) from membrane fractions prepared from the erythrocytes. Although 192 fmoles/mg of protein of (-)-[3H]dihydroalprenolol binding sites were lost from the membranes of desensitized cells, only 24 fmoles/mg of protein of [3H]hydroxybenzylisoproterenol remained specifically bound to sites in the membranes from the desensitized cells. Thus residual agonist, tightly bound to "high-affinity" receptor sites, does not explain the loss of beta adrenergic receptor binding sites that occurs during desensitization of the intact cells. ER -