Abstract
Opioid receptors are involved in regulating neuronal survival. Here we demonstrate that activation of the mu-opioid receptor in human neuroblastoma SH-SY5Y cells led to the phosphorylations of IkappaB kinase (IKK) and p65, denoting the stimulation of the nuclear factor-kappaB (NFkappaB) transcription factor. This response was mediated through pertussis toxin-sensitive G proteins. The mu-opioid-induced IKK phosphorylation required extracellular signal-regulated protein kinase, phosphatidylinositol 3-kinase and c-Src. Moreover, c-Jun N-terminal kinase and calmodulin-dependent kinase II also participated in the IKK activation, despite the lack of involvement of phospholipase Cbeta and protein kinase C. These data suggest that the mu-opioid receptor is capable of simulating NFkappaB signaling via the phosphorylation of IKK and p65 in human neuroblastoma SH-SY5Y cells.
Copyright 2005 S. Karger AG, Basel.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics, Opioid / pharmacology
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Analysis of Variance
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Blotting, Western / methods
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Drug Interactions
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
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Enzyme Inhibitors / pharmacology
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Humans
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Mitogen-Activated Protein Kinases / metabolism*
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Naloxone / pharmacology
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Narcotic Antagonists / pharmacology
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Neuroblastoma / metabolism*
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Pertussis Toxin / pharmacology
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Phosphorylation / drug effects
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Receptors, Opioid, mu / physiology*
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Somatostatin / analogs & derivatives
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Somatostatin / pharmacology
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Time Factors
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eIF-2 Kinase / metabolism
Substances
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Analgesics, Opioid
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Enzyme Inhibitors
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Narcotic Antagonists
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
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Naloxone
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Somatostatin
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Pertussis Toxin
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eIF-2 Kinase
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Mitogen-Activated Protein Kinases