Molecular Pharmacology, Vol 11, 866-873, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Glutamate-Elicited Accumulation of Adenosine Cyclic 3',5'-Monophosphate in Brain Slices by ,-Diaminocarboxylic Acids

¹ Department of Pharmacology and Biochemistry, Nippon Roche Research Center, Kajiwara, Kamakura, Japan

The accumulation of cyclic 3',5'-AMP elicited by glutamate in incubated slices of guinea pig cerebral cortex was inhibited by 2,3-diaminopropionate, 2,4-diaminobutyrate, or ornithine. The inhibitory action of histidine was marginal, and other basic amino acids, -monoamino acids, and aliphatic diamines were ineffective as inhibitors. 2,3-Diaminopropionate at 2 mM inhibited the stimulatory effect of glutamate more than 50% with respect to both endogenous and radioactive cyclic AMP; the latter was derived from intracellular nucleotides labeled during a prior incubation with radioactive adenine. Such a marked inhibitory action of 2,3-diaminopropionate was not observed toward the effects of adenosine, histamine, or a histamine-norepinephrine combination. 2'-Deoxyadenosine was found to be capable of inhibiting the adenosine effect, using either the radioactive labeling assay or the measurement of endogenous levels of cyclic AMP. The glutamate effect was not inhibited by the nucleoside. The results demonstrate that 2,3-diaminopropionic acid and 2'-deoxyadenosine are specific antagonists of the respective receptors, the former for acidic amino acids and the latter for adenosine, both of which mediate accumulation of cyclic AMP in incubated brain slices.

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ACKNOWLEDGMENTS We acknowledge the technical assistance of Miss Y. Mizokami and Miss S. Oikawa. We are also grateful to Dr. Y. Yagi and Dr. T. Yamada for their critical review of this paper.