Transient increase in intracellular concentration of adenosine 3':5'-cyclic monophosphate results in morphological and biochemical differentiation of C6 glioma cells in culture.

Incubation of C6-BU1 glioma cells in the presence of isoproterenol and Ro20-1724--a potent cAMP phosphodiesterase inhibitor--results in a transient increase in intracellular cAMP levels, followed by a rapid efflux of cyclic AMP from the cells into the media. Two distinct types of morphological changes could be seen: rounded cell bodies with multipolar processes and beadings after 30 minutes of incubation--this period coincides with a 70-80-fold increase in intracellular cAMP levels, and elongated cell bodies with extended bipolar processes after 24-48 hours. By this time the intracellular cAMP concentration dropped to a low level, which was only three- to four fold higher than that in control. The transient increase in intracellular cAMP concentration results in retardation of cell growth, diminished uptake of 3H-2-deoxyglucose, and abolition of enhanced synthesis of cyclic AMP by concanavalin A.