title: Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor.
abstract: 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.
authors.affiliation: Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, M5T 1R8, Ontario, Canada
authors.forename: Frank J S
authors.initials: FJ
authors.lastname: Lee
authors.forename: Sheng
authors.initials: S
authors.lastname: Xue
authors.forename: Lin
authors.initials: L
authors.lastname: Pei
authors.forename: Brian
authors.initials: B
authors.lastname: Vukusic
authors.forename: Nadege
authors.initials: N
authors.lastname: Chéry
authors.forename: Yushan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Niznik
authors.forename: Xian-min
authors.initials: XM
authors.lastname: Yu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008956:Models, Chemical; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001552:Benzazepines; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D000077191:Wortmannin; C409466:NR1 NMDA receptor; C067113:SK&F 81297