Specificity of putative partial agonist, 1-aminocyclopropanecarboxylic acid, for rat N-methyl-D-aspartate receptor subunits.
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 microM 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 microM NMDA. NR1-1a/NR2B and NR1-1a/NR2C subunit combinations yielded overlapping dose response curves with a maximal efficacy of approximately 80%; the maximal efficacy of ACPC for the NR1-1a/NR2A subunit combination was significantly lower at approximately 60%.
Sheinin
Anton
A
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
Nahum-Levy
Rinat
R
Shavit
Sara
S
Benveniste
Morris
M
D000598:Amino Acids, Cyclic / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000737:chemistry; D013379:Substrate Specificity; D014982:Xenopus laevis
D000598:Amino Acids, Cyclic; D018690:Excitatory Amino Acid Agonists; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D018696:Neuroprotective Agents; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C023863:1-aminocyclopropane-1-carboxylic acid; D016202:N-Methylaspartate; D005998:Glycine