Where Do You Think You Are Going? The NMDA-D1 Receptor Trap

Abstract

The number and outcomes of reciprocal interactions between dopamine (DA) D1 receptors and N-methyl-D-aspartate (NMDA)-type glutamate receptors continue to increase. Recent studies have demonstrated close physical interactions in which activation of one receptor affects the function of the other. In one physical interaction, the activation of NMDA receptors alters the topography and movement of D1 receptors by trapping them in dendritic spines and thus altering their distribution. In a second physical interaction, D1 and subunits of NMDA receptors form heterodimers, which are translocated from the cell interior to the surface. Finally, a third physical interaction posits that the C terminus of D1 receptors makes contact with subunits of the NMDA receptor. These physical interactions can attenuate or potentiate receptor function. In contrast, the more traditional interactions mediated by second messengers generally cause NMDA receptor function to be potentiated through the activation of D1 receptors and the cAMP-PKA-DARPP-32 [adenosine 3',5'-monophosphate (cAMP)-protein kinase A-cAMP-regulated phosphoprotein of 32 kD] or PKC (protein kinase C) cascades. Together, these mechanisms provide a basis for understanding the increasing complexity of D1-NMDA receptor interactions and their importance in physiological and pathological processes.