Relationship between an altered membrane form and a low affinity form of the beta-adrenergic receptor occurring during catecholamine-induced desensitization. Evidence for receptor internalization.

We have investigated the relationship between the catecholamine-induced occurrence in 1321N1 human astrocytoma cells of beta-adrenergic receptors that exhibit low apparent affinity for hydrophilic ligands in short-time assays with intact cells and a population of beta-adrenergic receptors that migrate in a light vesicle fraction on sucrose density gradients. Pretreatment of cells with concanavalin A prevents the generation of both of these forms of the receptor during incubation with agonists but does not prevent the agonist-induced decrease in isoproterenol-stimulated cyclic AMP production that also occurs during desensitization. Selective labeling of the low affinity beta-receptors with 125I-pindolol followed by centrifugation on sucrose density gradients revealed that all of the receptors in the light vesicle fraction from desensitized cells were of the low affinity type, but that a portion of the low affinity receptors also migrated in a heavier sucrose fraction together with the plasma membrane. In contrast, in control cells, no low affinity receptors were present in the heavy sucrose fractions. The agonist-induced occurrence of these various forms of the beta-adrenergic receptor can be explained on the basis of current models of desensitization involving agonist-induced internalization of beta-adrenergic receptors.