Characterization of agonist-induced beta-adrenergic receptor-specific desensitization in C62B glioma cells

The characteristics of catecholamine-induced desensitization of the beta-adrenergic receptor-linked adenylate cyclase system is compared in C62B and C6BD12 rat glioma cells and 1321N1 human astrocytoma cells. The process of receptor-specific (or agonist-specific) desensitization is demonstrated in the C62B subline. Thus, upon exposure of C62B cells to catecholamine a rapid decline (t 1/2 = 6-8 min) in isoproterenol-stimulated adenylate cyclase activity occurs with minimal loss in basal or NaF-stimulated activity. With the same time course an uncoupled population of beta-receptors is formed and can be isolated as a low density, particulate subfraction of cell lysates. These early desensitization processes are not blocked by cycloheximide. With extended exposure to catecholamines beta-receptors are lost from detection with a t 1/2 of 150-180 min. This process in C62B cells exhibits the same characteristics observed by others for other sublines of C6 cells (Homburger, et al. J. Biol. Chem. 255: 10436, 1980; and Fishman, et al. Mol. Pharmacol. 20: 310, 1981) and by us for human astrocytoma cells (Su et al. J. Biol. Chem. 255: 7410, 1980). In addition, the existence in C62B cells of a cyclic AMP-induced, cycloheximide-sensitive desensitization process, such as that reported by others (Terasaki, et al. Adv. Cyclic Nuc. Res. 9: 33, 1978) is confirmed. Thus, it appears that C62B cells exhibit all of the characteristics typically attributed to receptor-specific desensitization in addition to the cyclic AMP-mediated heterologous process described previously.