κ-Opioid modulation of human microglial cell superoxide anion generation

Shuxian Hu, Phillip K. Peterson, Chun C. Chao

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Opioids have been postulated to play an immunomodulatory role in the CNS. Recently, we found that priming microglia with interferon (IFN)-γ or tumor necrosis factor (TNF)-α resulted in an enhanced production of superoxide anion, a reactive oxygen intermediate that may be pathogenic during brain inflammation. In the present study, we investigated the effects of trans-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488), a selective κ-opioid ligand, on microglial cell superoxide production when cells were primed with cytokines or stimulated with phorbol myristate acetate. While treatment of microglial cells with U50,488 had little effect on nonstimulated or stimulated superoxide production, this opioid inhibited (by >70%) the priming effects of cytokines. Maximal inhibition of microglial cell superoxide generation by U50,488 was observed at 10 nM for the priming effect of interferon-γ and at 1 μM for tumor necrosis factor-α. Pretreatment of microglial cell cultures for 30 min with an equal concentration of the selective κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) completely blocked the inhibitory effect of U50,488. The results of this study suggest that κ-opioids may have therapeutic potential in inflammatory diseases of the CNS involving reactive oxygen intermediates produced by activated microglia. Copyright (C) 1998 Elsevier Science, Inc.

Original languageEnglish (US)
Pages (from-to)285-288
Number of pages4
JournalBiochemical Pharmacology
Volume56
Issue number3
DOIs
StatePublished - Aug 1 1998

Bibliographical note

Funding Information:
This work was supported, in part, by U.S. Public Health Service Grants DA09924 and DA04381 from the National Institute on Drug Abuse.

Keywords

  • Brain
  • Inflammation
  • Interferon
  • Reactive oxygen intermediate
  • Tumor necrosis factor

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