Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Proteome Res
2006 Apr 01;54:1017-23. doi: 10.1021/pr060016+.
Show Gene links
Show Anatomy links
Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity.
Woods AS
,
Kaminski R
,
Oz M
,
Wang Y
,
Hauser K
,
Goody R
,
Wang HY
,
Jackson SN
,
Zeitz P
,
Zeitz KP
,
Zolkowska D
,
Schepers R
,
Nold M
,
Danielson J
,
Gräslund A
,
Vukojevic V
,
Bakalkin G
,
Basbaum A
,
Shippenberg T
.
???displayArticle.abstract??? Prodynorphin-derived peptides elicit various pathological effects including neurological dysfunction and cell death. These actions are reduced by N-methyl-d-aspartate receptor (NMDAR) but not opioid receptor antagonists suggesting NMDAR-mediation. Here, we show that a conserved epitope (KVNSEEEEEDA) of the NR1 subunit of the NMDAR binds dynorphin peptides (DYNp) noncovalently. Synthetic peptides containing this epitope form stable complexes with DYNp and prevent the potentiation of NMDAR-gated currents produced by DYNp. They attenuate DYNp-evoked cell death in spinal cord and prevent, as well as reverse, DYNp-induced paralysis and allodynia. The data reveal a novel mechanism whereby prodynorphin-derived peptides facilitate NMDAR function and produce neurotoxicity. Furthermore, they suggest that synthetic peptides that bind DYNp, thus preventing their interaction with NMDAR, may be novel therapeutic agents for the treatment of spinal cord injury.
???displayArticle.pubmedLink???
16602711
???displayArticle.pmcLink???PMC2538681 ???displayArticle.link???J Proteome Res ???displayArticle.grants???[+]
Bakshi,
Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis.
1990, Pubmed
Bakshi,
Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis.
1990,
Pubmed
Caudle,
Dynorphin: friend or foe?
2000,
Pubmed
Caudle,
Intrathecal dynorphin(1-13) results in an irreversible loss of the tail-flick reflex in rats.
1987,
Pubmed
Caudle,
A novel interaction between dynorphin(1-13) and an N-methyl-D-aspartate site.
1988,
Pubmed
Danielsson,
The Alzheimer beta-peptide shows temperature-dependent transitions between left-handed 3-helix, beta-strand and random coil secondary structures.
2005,
Pubmed
Faden,
Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury.
1985,
Pubmed
Hauser,
Structure-activity analysis of dynorphin A toxicity in spinal cord neurons: intrinsic neurotoxicity of dynorphin A and its carboxyl-terminal, nonopioid metabolites.
2001,
Pubmed
Hauser,
Pathobiology of dynorphins in trauma and disease.
2005,
Pubmed
Hauser,
Dynorphin A (1-13) neurotoxicity in vitro: opioid and non-opioid mechanisms in mouse spinal cord neurons.
1999,
Pubmed
Herman,
Antinociception and paralysis induced by intrathecal dynorphin A.
1985,
Pubmed
Jackson,
Phosphate stabilization of intermolecular interactions.
2006,
Pubmed
Laughlin,
Mechanisms of induction of persistent nociception by dynorphin.
2001,
Pubmed
Long,
Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. II. Nonopioid mechanisms mediate loss of motor, sensory and autonomic function.
1988,
Pubmed
Long,
Dynorphin A-induced rat hindlimb paralysis and spinal cord injury are not altered by the kappa opioid antagonist nor-binaltorphimine.
1989,
Pubmed
Malan,
Extraterritorial neuropathic pain correlates with multisegmental elevation of spinal dynorphin in nerve-injured rats.
2000,
Pubmed
McIntosh,
Alterations in regional concentrations of endogenous opioids following traumatic brain injury in the cat.
1987,
Pubmed
Ossipov,
Induction of pain facilitation by sustained opioid exposure: relationship to opioid antinociceptive tolerance.
2003,
Pubmed
Piehl,
Calcitonin gene-related peptide-like immunoreactivity in motoneuron pools innervating different hind limb muscles in the rat.
1993,
Pubmed
Ren,
An improved method for assessing mechanical allodynia in the rat.
1999,
Pubmed
Shukla,
Nonopioid motor effects of dynorphin A and related peptides: structure dependence and role of the N-methyl-D-aspartate receptor.
1997,
Pubmed
Supplisson,
Control of NMDA receptor activation by a glycine transporter co-expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Tachibana,
Dynorphin mRNA expression in dorsal horn neurons after traumatic spinal cord injury: temporal and spatial analysis using in situ hybridization.
1998,
Pubmed
Vanderah,
Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone.
1996,
Pubmed
Woods,
A study of peptide--peptide interaction by matrix-assisted laser desorption/ionization.
2001,
Pubmed
Woods,
A study of peptide-peptide interactions using MALDI ion mobility o-TOF and ESI mass spectrometry.
2002,
Pubmed
Woods,
The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: their role in the noncovalent minuet.
2004,
Pubmed
Woods,
Role of electrostatic interaction in receptor-receptor heteromerization.
2005,
Pubmed
Woods,
Amazing stability of the arginine-phosphate electrostatic interaction.
2005,
Pubmed
Zhang,
Potentiation of NMDA receptor-mediated responses by dynorphin at low extracellular glycine concentrations.
1997,
Pubmed
,
Xenbase
