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Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice
DC Field | Value | Language |
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dc.contributor.author | Kim, H-W | - |
dc.contributor.author | Roh, D-H | - |
dc.contributor.author | Yoon, Seo Yeon | - |
dc.contributor.author | Seo, H-S | - |
dc.contributor.author | Kwon, Y-B | - |
dc.contributor.author | Han, H-J | - |
dc.contributor.author | Kim, K-W | - |
dc.contributor.author | Beitz, AJ | - |
dc.contributor.author | Lee, J-H | - |
dc.date.accessioned | 2009-08-31T23:23:44Z | - |
dc.date.available | 2009-08-31T23:23:44Z | - |
dc.date.issued | 2008-05-19 | - |
dc.identifier.citation | Br J Pharmacol 154: 1125-1134 | en |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | https://hdl.handle.net/10371/8274 | - |
dc.description.abstract | Background and purpose: Previously we demonstrated that the spinal sigma-1 receptor (Sig-1 R) plays an important role in
pain transmission, although the exact mechanism is still unclear. It has been suggested that Sig-1 R agonists increase glutamate-induced calcium influx through N-methyl-D-aspartate (NMDA) receptors. Despite data suggesting a link between Sig-1 Rs and NMDA receptors, there are no studies addressing whether Sig-1 R activation directly affects NMDA receptor sensitivity. Experimental approach: We studied the effect of intrathecal (i.t.) administration of Sig-1 R agonists on protein kinase C (PKC) and protein kinase A (PKA) dependent phosphorylation of the NMDA receptor subunit NR1 (pNR1) as a marker of NMDA receptor sensitization. In addition, we examined whether this Sig-1 R mediated phosphorylation of NR1 plays an important role in sensory function using a model of NMDA-induced pain. Key results: Both Western blot assays and image analysis of pNR1 immunohistochemical staining in the spinal cord indicated that i.t. injection of the Sig-1 R agonists, PRE-084 or carbetapentane dose dependently enhanced pNR1 expression in the murine dorsal horn. This increased pNR1 expression was significantly reduced by pretreatment with the specific Sig-1 R antagonist, BD-1047. In another set of experiments Sig-1 R agonists further potentiated NMDA-induced pain behaviour and pNR1 immunoreactivity and this was also reversed with BD-1047. Conclusions and implications: The results of this study suggest that the activation of spinal Sig-1 R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR 1 subunit. | en |
dc.description.sponsorship | This work was supported by a grant (R01-2005-000-10580-0)
from the Basic Research Program of the Korea Science & Engineering Foundation. In addition, it was also supported by a grant (M103KV010016-07K2201-01610) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea. | en |
dc.language.iso | en | - |
dc.publisher | Wiley-Blackwell | en |
dc.publisher | The British Pharmacological Society | - |
dc.subject | sigma-1 receptor | en |
dc.subject | NMDA receptor | en |
dc.subject | NR1 subunit | en |
dc.subject | phosphorylation | en |
dc.subject | pain | en |
dc.subject | mice | en |
dc.title | Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이장헌 | - |
dc.identifier.doi | 10.1038/bjp.2008.159 | - |
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