Adaptive changes in the responsiveness of adenylate cyclase to catecholamines

Exposure of the intact astrocytoma cell to isoproterenol not only causes the activation of adenylate cyclase and the accumulation of cyclic AMP but sets in motion a complicated series of events designed to down-regulate the system if exposure to the agonist is extended in time. We have identified at least three of these processes: (1) a rapid uncoupling of the beta-receptor--adenylate cyclase system with subsequent loss of beta-receptors; (2) a slower, nonspecific desensitization of adenylate cyclase to the effects of all classes of receptor agonists by a process that may be mediated by cyclic AMP; and (3) a slow induction of phosphodiesterase activity that is probably mediated by cyclic AMP.