ELEVATION OF CYCLIC GMP LEVELS IN CENTRAL NERVOUS SYSTEM BY EXCITATORY AND INHIBITORY AMINO ACIDS¹

Abstract

Abstract —Guanosine 3′,5’cyclic monophosphate (cyclic GMP) levels in incubated slices of mouse cerebellum are increased 10‐fold by glutamate and two‐to three‐fold by glycine or γ‐aminobutyric acid (GABA). Glutamate also produces a 10‐fold increase in adenosine 3′,5’cyclic monophosphate (cyclic AMP) in the same tissue. However, GABA decreases cyclic AMP levels 30‐40 per cent, and glycine produces only a transient 50 per cent accumulation of this cyclic nucleotide. Theophylline slightly augments the accumulation of cyclic GMP produced by all three amino acids but markedly attenuates the accumulation of cyclic AMP produced by glutamate. In the absence of Ca 2+ , none of the three amino acids has any effect on cyclic GMP levels, and glutamate produces only a 50 per cent rise in cyclic AMP levels. The decrease of cyclic AMP levels produced by GABA is not affected by theophylline or by the absence of Ca 2+ . These data suggest an involvement of both cyclic GMP and cyclic AMP in the neurochemical actions of glutamate, GABA and glycine.