Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor.
Dopamine D1-like receptors, composed of D1 and D5 receptors, have been documented to modulate glutamate-mediated fast excitatory synaptic neurotransmission. Here, we report that dopamine D1 receptors modulate NMDA glutamate receptor-mediated functions through direct protein-protein interactions. Two regions in the D1 receptor carboxyl tail can directly and selectively couple to NMDA ... glutamate receptor subunits NR1-1a and NR2A. While one interaction is involved in the inhibition of NMDA receptor-gated currents, the other is implicated in the attenuation of NMDA receptor-mediated excitotoxicity through a PI-3 kinase-dependent pathway.
Mesh Terms:
Androstadienes, Animals, Apoptosis, Benzazepines, Blotting, Western, Cells, Cultured, Corpus Striatum, Enzyme Inhibitors, Hippocampus, Models, Chemical, Phosphatidylinositol 3-Kinases, Rats, Receptors, Dopamine D1, Receptors, N-Methyl-D-Aspartate
Androstadienes, Animals, Apoptosis, Benzazepines, Blotting, Western, Cells, Cultured, Corpus Striatum, Enzyme Inhibitors, Hippocampus, Models, Chemical, Phosphatidylinositol 3-Kinases, Rats, Receptors, Dopamine D1, Receptors, N-Methyl-D-Aspartate
Cell
Date: Oct. 18, 2002
PubMed ID: 12408866
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