Mu-opioid receptor-mediated phosphorylation of IkappaB kinase in human neuroblastoma SH-SY5Y cells

Neurosignals. 2005;14(3):136-42. doi: 10.1159/000086296.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Analysis of Variance
  • Blotting, Western / methods
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neuroblastoma / metabolism*
  • Pertussis Toxin / pharmacology
  • Phosphorylation / drug effects
  • Receptors, Opioid, mu / physiology*
  • Somatostatin / analogs & derivatives
  • Somatostatin / pharmacology
  • Time Factors
  • eIF-2 Kinase / metabolism

Substances

  • Analgesics, Opioid
  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
  • Naloxone
  • Somatostatin
  • Pertussis Toxin
  • eIF-2 Kinase
  • Mitogen-Activated Protein Kinases