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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Animals
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Apoptosis
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Benzazepines / pharmacology
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Blotting, Western
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Cells, Cultured
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Corpus Striatum / metabolism
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Enzyme Inhibitors / pharmacology
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Hippocampus / metabolism
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Models, Chemical
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Phosphoinositide-3 Kinase Inhibitors
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Rats
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Receptors, Dopamine D1 / metabolism*
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Wortmannin
Substances
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Androstadienes
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Benzazepines
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Enzyme Inhibitors
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NR1 NMDA receptor
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Phosphoinositide-3 Kinase Inhibitors
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Receptors, Dopamine D1
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Receptors, N-Methyl-D-Aspartate
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SK&F 81297
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N-methyl D-aspartate receptor subtype 2A
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Wortmannin