1‐Aminocyclopropane Carboxylic Acid: A Potent and Selective Ligand for the Glycine Modulatory Site of the N‐Methyl‐d‐Aspartate Receptor Complex

Abstract

1-Aminocyclopropane carboxylic acid (ACPC) competitively inhibited (IC₅₀, 38 ± 7 nM) [³H]glycine binding to rat forebrain membranes but did not affect [³H]strychnine binding to rat brainstem/ spinal cord membranes. Like glycine, ACPC enhanced ³H-labelled (+)-5-methyl-10,11 -dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate ([³H]MK-801) binding to TV-methyl-D-aspartate receptor-coupled cation channels (EC₅₀, 135 ± 76 nM and 206 ± 78 nM for ACPC and glycine, respectively) but was ∼ 40% less efficacious in this regard. The maximum increase in [³H]MK-801 binding produced by a combination of ACPC and glycine was not different from that elicited by glycine, but both compounds potentiated glutamate-stimulated [³H]MK-801 binding. These findings indicate that ACPC is a potent and selective ligand at the glycine modulatory site associated with the N-methyl-d-aspartate receptor complex.