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

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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.