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

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

Robarts Research Institute, Molecular Brain Research Group, University of Western Ontario, 100 Perth Drive, London, ON N6A 5K8, Canada
Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB R3E 0T6, Canada
Neuroscience Research Group, Kleysen Institute for Advanced Medicine, Health Sciences Centre, University of Manitoba, Winnipeg, MB R3E 3J7, Canada
Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5K8, Canada
Present address: Brain Research Centre, 2211 Wesbrook Mall, University of British Columbia, Vancouver, BC V6T 2B5, Canada
Authors to whom correspondence should be addressed.
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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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. View Full-Text
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 (CC BY 3.0).

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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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