INFLUENCE OF DIVALENT CATIONS ON REGULATION OF CYCLIC GMP AND CYCLIC AMP LEVELS IN BRAIN TISSUE |
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Authors: | J. A. Ferrendelli E. H. Rubin Dorothy A. Kinscherf |
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Affiliation: | Departments of Pharmacology and Neurology, Washington University School of Medicine. 660 S. Euclid Ave., St. Louis, MO 63110, U.S.A. |
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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 mm or 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. |
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