Effect of sodium ion on levels of cyclic adenosine 3',5'-monophosphate in guinea pig cerebral slices.

Accumulation of cyclic AMP was studied in guinea pig cerebral slices when Na+ levels in the bathing medium were varied or agents which affect tissue Na+ content were added. When NaCl was gradually replaced with Tris-HCl or choline chloride, cyclic AMP formation was progressively enhanced. ;when Na+ was below 30 mM, cyclic AMP formation reached the maximum (approximately 30 fold), but this increment was not blocked by tetrodotoxin. The stimulatory effect of high K+ was nearly linear over 120 mM and became much more prominent when Na+ also was not blocked by tetrodotoxin. Ouabain (10(-4) M), electrical pulses and glutamate (5 x 10(-3) M), each stimulated cyclic AMP formation about 17-, 7- and 5-fold, respectively. Tetrodotoxin (2 x 10(-6) M) completely blocked the effects of electrical pulses and partially blocked the effects of glutamate and oubain. It is suggested that the increase of cyclic AMP in cerebral cortical slices may be related to the decrease in Na+ gradient across the cell membrane.