Stimulated formation of adenosine 3',5'-cyclic phosphate in cerebral cortex: synergism between electrical activity and biogenic amines.

When cortical slices are incubated with adenine-(14)C, adenine nucleotides are labeled in a small and relatively stable pool. The ATP-(14)C of this pool is readily converted to cAMP-(14)C during incubations with depolarizing agents, such as K(+), ouabain, veratridine, or batrachotoxin. During incubations with these agents, release of acetylcholine and of adenosine into the medium is enhanced. The increase in release of adenosine parallels the enhanced formation of cAMP-(14)C elicited by depolarizing agents, providing further evidence that adenosine may serve to couple electrical activity in the central nervous system with formation of cAMP. When adenosine or a depolarizing agent are incubated, together with a biogenic amine, such as histamine, serotonin, or norepinephrine, the combined effect on cAMP-(14)C formation in cortical slices is much more than additive. Extracellular levels of biogenic amines could in this manner modulate cAMP formation and biochemical responses in nervous tissue during electrical activity.