EFFECT OF 1-AMINOCYCLOPROPANECARBOXYLIC ACID ON N-METHYL-D-ASPARTATE-STIMULATED [H-3] NORADRENALINE RELEASE IN RAT HIPPOCAMPAL SYNAPTOSOMES

1 The effect of 1-aminocyclopropanecarboxylic acid (ACPC), a partial a gonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant- like actions, was investigated in a functional assay for presynaptic N MDA receptors. 2 NMDA (100 mu M) produced a 36% increase of tritium ef flux above basal efflux in rat hippocampal synaptosomes preincubated w ith [H-3]-noradrenaline ([H-3]-NA), reflecting a release of tritiated noradrenaline. This effect was prevented by 10 mu M 7-chlorokynurenic acid, an antagonist of the glycine site of the NMDA receptor. 3 Glycin e enhanced the effect of NMDA with E(max) and EC(50) values of 84+/-11 % and 1.82+/-0.04 mu M, respectively. ACPC potentiated the effect of N MDA on tritium overflow with a lower EC(50) (43+/-6 nM) and a lower ma ximal effect (E(max) = 40+/-9%) than glycine. Furthermore, ACPC (0.1 m u M) shifted the EC(50) of glycine from 1.82 mu M to greater than or e qual to 3 mM. 4 These results show that ACPC can reduce the potentiati on by glycine of NMDA-evoked [H-3]-NA release and hence, may act as an antagonist at the glycine site of presynaptic hippocampal NMDA recept ors when the concentration of glycine is high.