Influence of Divalent Cations on Regulation of Cyclic GMP and Cyclic Amp Levels in Brain Tissue

Abstract —Depolarizing concentrations of K+elevate levels of both adenosine 3′,5′monophosphate (cyclic AMP) and guanosine 3′,5′monophosphate (cyclic GMP) in incubated slices of mouse cerebellum. Calcium is an essential requirement for the K+‐induced accumulation of cyclic GMP. Barium and Sr2+, but not Mn2+or Co2+, can substitute for Ca2+in this process. Relatively high concentrations of Mg2+inhibit the effect of Ca2+on K+‐induced accumulation of cyclic GMP. In contrast, depolarizing concentrations of K+are capable of elevating cyclic AMP levels in brain slices suspended in media containing Mg2+and no other divalent cations. High concentrations of Ca2+(1 mmor greater) augment this Mg2+‐dependent, K+‐induced accumulation of cyclic AMP, however. Strontium and Mn2+, but not Ba2+or Co2+, can substitute for Ca2+in this process, and high concentrations of Mg2+are not inhibitory. The divalent cation ionophore, A‐23187 (10 μm), in the presence of extracellular Ca2+elevates the level of cyclic GMP, but not cyclic AMP, in incubated mouse cerebellum slices. The results of this study indicate that intracellular Ca2+concentration is a major factor regulating cyclic GMP levels in brain. In addition the present results suggest that, in brain tissue, depolarization‐induced accumulation of cyclic GMP, but not cyclic AMP, is closely linked to some Ca2+‐dependent mechanism(s) mediating release of intracellular substances.