| First Author | Pabba M | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 34 | Pages | 11325-38 |
| PubMed ID | 25143613 | Mgi Jnum | J:216165 |
| Mgi Id | MGI:5607821 | Doi | 10.1523/JNEUROSCI.0458-14.2014 |
| Citation | Pabba M, et al. (2014) NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus. J Neurosci 34(34):11325-38 |
| abstractText | Sigma-1 receptors (sigma-1Rs) are endoplasmic reticulum resident chaperone proteins implicated in many physiological and pathological processes in the CNS. A striking feature of sigma-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 sigma-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 sigma-1R agonists (+)-SKF 10,047 [2S-(2alpha,6alpha,11R*]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-m ethano-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 sigma-1R activation leads to an increased interaction between GluN2 subunits and sigma-1Rs and mediates trafficking of NMDARs to the cell surface. These results suggest that sigma-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. |
