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 agonist 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 NMDA receptors. 2 NMDA (100 mu M) produced a 36% increase of tritium efflux above basal efflux in rat hippocampal synaptosomes preincubated with [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 Glycine 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 NMDA on tritium overflow with a lower EC(50) (43+/-6 nM) and a lower maximal effect (E(max) = 40+/-9%) than glycine. Furthermore, ACPC (0.1 mu M) shifted the EC(50) of glycine from 1.82 mu M to greater than or equal to 3 mM. 4 These results show that ACPC can reduce the potentiation by glycine of NMDA-evoked [H-3]-NA release and hence, may act as an antagonist at the glycine site of presynaptic hippocampal NMDA receptors when the concentration of glycine is high.