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.
D000262:Adenylyl Cyclases / Q000032:analysis / Q000502:physiology*; D000818:Animals; D001254:Astrocytoma / Q000201:enzymology; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D000242:Cyclic AMP / Q000032:analysis / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D003513:Cycloheximide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol