Stimulated Formation of Cyclic Adenosine 3′:5′-Monophosphate by Aspartate and Glutamate in Cerebral Cortical Slices of Guinea Pig

Abstract

Abstract The content of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in guinea pig cerebral cortical slices increases approximately 40-fold during a 10-min incubation and 80-fold during a 20-min incubation in a medium containing 10mm l-glutamate. A similar increase was observed in levels of radioactive cyclic AMP derived from intracellular adenine nucleotides, labeled by a prior incubation with radioactive adenine. The stimulatory effect of l-glutamate on formation of radioactive cyclic AMP was found with a concentration as low as 0.05 mm, and concentrations of l-glutamate required for the half-maximal and maximal effects were about 1.5 and 10 mm, respectively. At 10 mm concentration, l-aspartate was as good as, and d-aspartate, d-glutamate, dl-α-aminoadipate, and l-alanine were weaker than, l-glutamate as a stimulant for the cyclic AMP formation. All other amino acids and metabolites of glutamic acid tested were virtually ineffective. Mutual potentiation of effects was observed when aspartate was added together with either adenosine or histamine, but not with glutamate, veratridine, or ouabain. The effect of the two amino acids were completely blocked by theophylline, but not by omission of Ca2+ or by addition of cocain, the conditions known to inhibit the depolarization-elicited formation of cyclic AMP. The formation of radioactive cyclic AMP stimulated by l-glutamate was allowed to return to a half of the stimulated levels within 20 min after removal of the glutamate by washing, and then was restimulated either by adenosine, l-aspartate, or l-glutamate. These properties of the amino acids suggest that the amino acids may be a new class of stimulants which is different from biogenic amines, adenosine, and depolarizing agents as stimulants for cyclic AMP formation in incubated brain slices.