1-Aminocyclopropane carboxylic acid: a potent and selective ligand for the glycine modulatory site of the N-methyl-D-aspartate receptor complex.
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 N-methyl-D-aspartate receptor-coupled cation channels (EC50, 135 +/- 76 nM and 206 +/- 78 nM for ACPC and glycine, respectively) but was approximately 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.
Marvizón
J C
JC
Laboratory of Neuroscience, NIDDK, Bethesda, MD 20892.
Lewin
A H
AH
Skolnick
P
P
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D001667:Binding, Competitive; D001933:Brain Stem / Q000378:metabolism; D002412:Cations; D003986:Dibenzocycloheptenes / Q000378:metabolism; D004027:Diencephalon / Q000378:metabolism; D016291:Dizocilpine Maleate; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013331:Strychnine / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D002412:Cations; D003986:Dibenzocycloheptenes; D005971:Glutamates; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C023863:1-aminocyclopropane-1-carboxylic acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D013331:Strychnine; D005998:Glycine