Extracellular cAMP accumulation and degradation in rat cerebral cortex in dissociated cell culture

Norepinephrine (NE) stimulated the accumulation of cAMP in embryonic rat cerebral cortex in dissociated cell culture. After exposure to NE for 10 min, the intracellular cAMP content of these cultures went from 22 +/- 12 to 202 +/- 75 pmol/mg protein. Using selective culturing techniques, evidence was obtained supporting the hypothesis that NE-stimulated production of cAMP is a property associated with the glial rather than the neuronal component of these cultures. Beta adrenergic agonist stimulation of cortical cultures also resulted in the efflux of cAMP into the medium. At the peak of extracellular accumulation of cAMP (following a 40-min exposure to isoproterenol), 180 pmol cAMP/mg protein had been transported into the extracellular medium. The fate of extracellular cAMP was investigated using thin-layer chromatography. Extracellular cAMP was degraded to AMP and adenosine; this degradation did not seem to be due to the presence of serum or serum components, suggesting the existence of an extracellular phosphodiesterase. In response to NE stimulation of glia, in particular astrocytes, cAMP or its metabolites may accumulate at high enough concentrations in the extracellular space in cerebral cortex to affect neuronal function, possibly via adenosine receptors.