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Effect of 1‐aminocyclopropanecarboxylic acid on N‐methyl‐ d ‐aspartate‐stimulated [ 3 H]‐noradrenaline release in rat hippocampal synaptosomes
Author(s) -
Clos M.V.,
Sanz A. Garcia,
Trullas R.,
Badia A.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15484.x
Subject(s) - nmda receptor , glycine , chemistry , agonist , glycine receptor , partial agonist , hippocampal formation , pharmacology , receptor , biochemistry , endocrinology , amino acid , biology
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 μ m ) produced a 36% increase of tritium efflux above basal efflux in rat hippocampal synaptosomes preincubated with [ 3 H]‐noradrenaline ([ 3 H]‐NA), reflecting a release of tritiated noradrenaline. This effect was prevented by 10 μ 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 μ 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 μ m ) shifted the EC 50 of glycine from 1.82 μ m to ≥ 3 mM. 4 These results show that ACPC can reduce the potentiation by glycine of NMDA‐evoked [ 3 H]‐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.