Indole-2-carboxylic acid: a competitive antagonist of potentiation by glycine at the NMDA receptor.
The N-methyl-D-aspartate (NMDA) class of excitatory amino acid receptors regulates the strength and stability of excitatory synapses and appears to play a major role in excitotoxic neuronal death associated with stroke and epilepsy. The conductance increase gated by NMDA is potentiated by the amino acid glycine, which acts at an allosteric site tightly coupled to the NMDA receptor. Indole-2-carboxylic acid (I2CA) specifically and competitively inhibits the potentiation by glycine of NMDA-gated current. In solutions containing low levels of glycine, I2CA completely blocks the response to NMDA, suggesting that NMDA alone is not sufficient for channel activation. I2CA will be useful for defining the interaction of glycine with NMDA receptors and for determining the in vivo role of glycine in excitotoxicity and synapse stabilization.
Huettner
J E
JE
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000502:physiology; D002264:Carboxylic Acids; D002478:Cells, Cultured; D004553:Electric Conductivity; D005998:Glycine / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D016202:N-Methylaspartate; D009433:Neural Inhibition; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D007211:Indoles; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C058980:indole-2-carboxylic acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D005998:Glycine