NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus.

Sigma-1 receptors (?-1Rs) are endoplasmic reticulum resident chaperone proteins implicated in many physiological and pathological processes in the CNS. A striking feature of ?-1Rs is their ability to interact and modulate a large number of voltage- and ligand-gated ion channels at the plasma membrane. We have reported previously that agonists ...
for ?-1Rs potentiate NMDA receptor (NMDAR) currents, although the mechanism by which this occurs is still unclear. In this study, we show that in vivo administration of the selective ?-1R agonists (+)-SKF 10,047 [2S-(2?,6?,11R*]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol hydrochloride (N-allylnormetazocine) hydrochloride], PRE-084 (2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate hydrochloride), and (+)-pentazocine increases the expression of GluN2A and GluN2B subunits, as well as postsynaptic density protein 95 in the rat hippocampus. We also demonstrate that ?-1R activation leads to an increased interaction between GluN2 subunits and ?-1Rs and mediates trafficking of NMDARs to the cell surface. These results suggest that ?-1R may play an important role in NMDAR-mediated functions, such as learning and memory. It also opens new avenues for additional studies into a multitude of pathological conditions in which NMDARs are involved, including schizophrenia, dementia, and stroke.
Mesh Terms:
Animals, Cell Membrane, Disks Large Homolog 4 Protein, Ethylenediamines, Hippocampus, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Mice, Mice, Knockout, Morpholines, Pentazocine, Phenazocine, Piperazines, Protein Transport, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Receptors, sigma, Sigma-1 Receptor, Subcellular Fractions, Time Factors, Up-Regulation
J Neurosci
Date: Aug. 20, 2014
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