Specificity of putative partial agonist, 1-aminocyclopropanecarboxylic acid, for rat N-methyl-d-aspartate receptor subunits

Abstract The neuroprotective compound, 1-aminocyclopropanecarboxylic acid (ACPC), has been reported to act on the N -methyl- d -aspartate (NMDA) receptors simultaneously as a glycine binding site agonist and a glutamate binding site competitive antagonist. The complex kinetics of NMDA current changes measured by a whole-cell voltage clamp in rat hippocampal neurons resulting from application and removal of 1 mM ACPC in the continual presence of 15 μM NMDA confirm this hypothesis. Two-electrode voltage clamp on Xenopus oocytes expressing NR1-1a and either NR2A, NR2B or NR2C subunits yielded biphasic ACPC dose response curves with 15 μM NMDA. NR1-1a/NR2B and NR1-1a/NR2C subunit combinations yielded overlapping dose response curves with a maximal efficacy of ∼80%; the maximal efficacy of ACPC for the NR1-1a/NR2A subunit combination was significantly lower at ∼60%.