Cepeda Carlos, Levine Michael S
Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA.
Sci STKE. 2006 May 2;2006(333):pe20. doi: 10.1126/stke.3332006pe20.
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.
多巴胺（DA）D1受体与N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体之间相互作用的数量和结果持续增加。最近的研究表明，它们之间存在紧密的物理相互作用，其中一种受体的激活会影响另一种受体的功能。在一种物理相互作用中，NMDA受体的激活通过将D1受体困在树突棘中从而改变其分布，进而改变D1受体的拓扑结构和移动。在第二种物理相互作用中，D1受体与NMDA受体的亚基形成异二聚体，这些异二聚体从细胞内部转运到细胞表面。最后，第三种物理相互作用认为D1受体的C末端与NMDA受体的亚基接触。这些物理相互作用可减弱或增强受体功能。相比之下，由第二信使介导的更传统的相互作用通常通过激活D1受体以及cAMP-PKA-DARPP-32[3',5'-环磷酸腺苷（cAMP）-蛋白激酶A-32kD的cAMP调节磷蛋白]或PKC（蛋白激酶C）级联反应来增强NMDA受体功能。总之，这些机制为理解D1-NMDA受体相互作用日益增加的复杂性及其在生理和病理过程中的重要性提供了基础。
