Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor

Cell. 2002 Oct 18;111(2):219-30. doi: 10.1016/s0092-8674(02)00962-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis
  • Benzazepines / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Corpus Striatum / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / metabolism
  • Models, Chemical
  • Phosphoinositide-3 Kinase Inhibitors
  • Rats
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Wortmannin


  • Androstadienes
  • Benzazepines
  • Enzyme Inhibitors
  • NR1 NMDA receptor
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • SK&F 81297
  • N-methyl D-aspartate receptor subtype 2A
  • Wortmannin