Effect of 1-aminocyclopropanecarboxylic acid on N-methyl-D-aspartate-stimulated [3H]-noradrenaline release in rat hippocampal synaptosomes

M. V. Clos, A. Garcia Sanz, R. Trullas, A. Badia

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9 Citations (Scopus)

Abstract

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 μM) produced a 36% increase of tritium efflux above basal efflux in rat hippocampal synaptosomes preincubated with [3H]-noradrenaline ([3H]-NA), reflecting a release of tritiated noradrenaline. This effect was prevented by 10 μM 7-chlorokynurenic acid, an antagonist of the glycine site of the NMDA receptor. 3. Glycine enhanced the effect of NMDA with E(max) and EC50 values of 84 ± 11% and 1.82 ± 0.04 μM, respectively. ACPC potentiated the effect, of NMDA on tritium overflow with a lower EC50 (43 ± 16 nM) and a lower maximal effect (E(max) = 40 ± 9%) than glycine. Furthermore, ACPC (0.1 μM) shifted the EC50 of glycine from 1.82 μM to ≤ 3 mM. 4. These results show that ACPC can reduce the potentiation by glycine of NMDA-evoked [3H]-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.
Original languageEnglish
Pages (from-to)901-904
JournalBritish Journal of Pharmacology
Volume118
Issue number4
DOIs
Publication statusPublished - 1 Jan 1996

Keywords

  • ACPC
  • Glycine
  • Hippocampus
  • NMDA receptor
  • Noradrenaline release

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