GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16190898

From GONUTS
Jump to: navigation, search
Citation

Abe, T, Matsumura, S, Katano, T, Mabuchi, T, Takagi, K, Xu, L, Yamamoto, A, Hattori, K, Yagi, T, Watanabe, M, Nakazawa, T, Yamamoto, T, Mishina, M, Nakai, Y and Ito, S (2005) Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain. Eur. J. Neurosci. 22:1445-54

Abstract

Despite abundant evidence implicating the importance of N-methyl-D-aspartate (NMDA) receptors in the spinal cord for pain transmission, the signal transduction coupled to NMDA receptor activation is largely unknown for the neuropathic pain state that lasts over periods of weeks. To address this, we prepared mice with neuropathic pain by transection of spinal nerve L5. Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury. Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase. Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry. Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice. Conversely, EP1-selective agonist stimulated Fyn kinase-dependent nitric oxide formation in the spinal cord. The present study demonstrates that Tyr1472 phosphorylation of NR2B subunits by Fyn kinase may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase, and suggests that PGE2 is involved in the maintenance of neuropathic pain via the EP1 subtype.

Links

PubMed Online version:10.1111/j.1460-9568.2005.04340.x

Keywords

Animals; Behavior, Animal/drug effects; Behavior, Animal/physiology; Blotting, Western; Dinoprostone/physiology; Dose-Response Relationship, Drug; Histocytochemistry; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Microscopy, Immunoelectron; Nitric Oxide/metabolism; Pain/etiology; Pain/physiopathology; Pain/psychology; Peripheral Nervous System Diseases/complications; Phosphorylation; Piperidines/pharmacology; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate/physiology; Signal Transduction/physiology; Tyrosine/metabolism; src-Family Kinases/physiology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

See Help:References for how to manage references in GONUTS.