Abstract

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.