ADENYLYL-CYCLASE ACTIVATION UNDERLIES INTRACELLULAR CYCLIC-AMP ACCUMULATION, CYCLIC-AMP TRANSPORT, AND EXTRACELLULAR ADENOSINE ACCUMULATIONEVOKED BY BETA-ADRENERGIC-RECEPTOR STIMULATION IN MIXED CULTURES OF NEURONS AND ASTROCYTES DERIVED FROM RAT CEREBRAL-CORTEX

We have previously shown that stimulation of cortical cultures contain ing both neurons and astrocytes with the beta-adrenergic agonist isopr oterenol (ISO) results in transport of cAMP from astrocytes followed b y extracellular hydrolysis to adenosine [Rosenberg et al. J. Neurosci. 14 (1994) 2953-2965]. In this study we found that the endogenous cate cholamines epinephrine (EPI) and norepinephrine (NE), but not dopamine , serotonin, or histamine, all at 10 mu M, significantly stimulated in tracellular cAMP accumulation, cAMP transport, and extracellular adeno sine accumulation in cortical cultures. Detailed dose-response experim ents were performed for NE and EPI, as well as ISO. For each catechola mine, the potencies in evoking intracellular cAMP accumulation, cAMP t ransport, and extracellular adenosine accumulation were similar. These data provide additional evidence that a single common mechanism, name ly beta-adrenergic mediated activation of adenylyl cyclase, underlies intracellular cAMP accumulation, cAMP transport, and extracellular ade nosine accumulation. It appears that regulation of extracellular adeno sine levels via cAMP transport and extracellular hydrolysis to adenosi ne may be a final common pathway of neuromodulation in cerebral cortex for catecholamines, and, indeed, any substance whose receptors are co upled to adenylyl cyclase.