Abstract

It has been proposed that electrical pulses and elevated levels of K⁺ ions and other ''depolarizing'' stimuli act to increase adenosine 3', 5'-monophosphate (cyclic AMP) levels in brain tissue via release and subsequent action of adenosine. This proposal was examined by comparing the effects of pulses and 40 mM KCl alone and in combination with adenosine and other agents in slices of guinea-pig cerebral cortex or cerebellum. Electrical pulses caused an increase in the cyclic AMP content of both cerebral cortex and cerebellar tissue; 40 mM KCl was only effective in the cortex. In the presence of maximally effective levels of adenosine, pulses had no additional effect in the cerebral cortex; however, in cerebellar slices an additional effect was observed. Tile combination of adenosine amid 40 mM KCl had a potentiative interaction in the cerebral cortex, while in the cerebellum this combination caused less accumulation of cyclic AMP than did adenosine alone. In cerebral cortical tissue the response to 40 mM KCl was blocked by 14 mM Mg⁺⁺ or the absence of calcium; however, the response to pulses was reduced only slightly by the absence of calcium and was undiminished in the presence of 14 mM Mg⁺⁺. It was concluded from these and other observations that electrical pulses and 40 mM KCl cannot be considered "identical stimuli" as far as the generation of cyclic AMP is concerned, that release of adenosine plays a variable role in the effect of these agents and that other factors must be involved.