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Int. J. Mol. Sci. 2014, 15(2), 3003-3024; doi:10.3390/ijms15023003
Review

Recent Progress in Understanding Subtype Specific Regulation of NMDA Receptors by G Protein Coupled Receptors (GPCRs)

1,†,* , 2,3,*  and 1,4
Received: 26 November 2013 / Revised: 30 December 2013 / Accepted: 12 February 2014 / Published: 20 February 2014
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract

G Protein Coupled Receptors (GPCRs) are the largest family of receptors whose ligands constitute nearly a third of prescription drugs in the market. They are widely involved in diverse physiological functions including learning and memory. NMDA receptors (NMDARs), which belong to the ionotropic glutamate receptor family, are likewise ubiquitously expressed in the central nervous system (CNS) and play a pivotal role in learning and memory. Despite its critical contribution to physiological and pathophysiological processes, few pharmacological interventions aimed directly at regulating NMDAR function have been developed to date. However, it is well established that NMDAR function is precisely regulated by cellular signalling cascades recruited downstream of G protein coupled receptor (GPCR) stimulation. Accordingly, the downstream regulation of NMDARs likely represents an important determinant of outcome following treatment with neuropsychiatric agents that target selected GPCRs. Importantly, the functional consequence of such regulation on NMDAR function varies, based not only on the identity of the GPCR, but also on the cell type in which relevant receptors are expressed. Indeed, the mechanisms responsible for regulating NMDARs by GPCRs involve numerous intracellular signalling molecules and regulatory proteins that vary from one cell type to another. In the present article, we highlight recent findings from studies that have uncovered novel mechanisms by which selected GPCRs regulate NMDAR function and consequently NMDAR-dependent plasticity.
Keywords: NMDA receptor; G protein coupled receptor; protein kinase A; protein kinase C; cyclic AMP NMDA receptor; G protein coupled receptor; protein kinase A; protein kinase C; cyclic AMP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Yang, K.; Jackson, M.F.; MacDonald, J.F. Recent Progress in Understanding Subtype Specific Regulation of NMDA Receptors by G Protein Coupled Receptors (GPCRs). Int. J. Mol. Sci. 2014, 15, 3003-3024.

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