β-funaltrexamine inhibits inducible nitric-oxide synthase expression in human astroglial cells

Randall Davis, Daniel J. Buck, Neda Saffarian, Shekher Mohan, Udaya DeSilva, Samodha C. Fernando, Craig Stevens

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon γ, tumor necrosis factor α, and interleukin-1β, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, β-funaltrexamine (β-FNA), on cytokine induced iNOS expression in human astroglia. β-FNA dose-dependently inhibited iNOS expression. β-FNA transcriptionally (or pre-transcriptionally) inhibited cytokine-induced iNOS activation as indicated by a significant decrease in NOS2 messenger RNA expression. Further characterization of the novel, anti-inflammatory actions of β-FNA may provide insights for pharmacologic strategies to treat or prevent brain pathologies associated with neuroinflammation.

Original languageEnglish
Pages (from-to)150-153
Number of pages4
JournalJournal of Neuroimmune Pharmacology
Volume3
Issue number3
DOIs
StatePublished - 1 Sep 2008

Fingerprint

Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Protein Isoforms
Cytokines
Astrocytes
Pathology
Narcotic Antagonists
mu Opioid Receptor
Brain Diseases
Interleukin-1
Interferons
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Messenger RNA
Brain
Infection

Keywords

  • Astrocytes
  • Fentanyl
  • Morphine
  • Neuroinflammation
  • Nitric oxide
  • Opioids

Cite this

Davis, Randall ; Buck, Daniel J. ; Saffarian, Neda ; Mohan, Shekher ; DeSilva, Udaya ; Fernando, Samodha C. ; Stevens, Craig. / β-funaltrexamine inhibits inducible nitric-oxide synthase expression in human astroglial cells. In: Journal of Neuroimmune Pharmacology. 2008 ; Vol. 3, No. 3. pp. 150-153.
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β-funaltrexamine inhibits inducible nitric-oxide synthase expression in human astroglial cells. / Davis, Randall; Buck, Daniel J.; Saffarian, Neda; Mohan, Shekher; DeSilva, Udaya; Fernando, Samodha C.; Stevens, Craig.

In: Journal of Neuroimmune Pharmacology, Vol. 3, No. 3, 01.09.2008, p. 150-153.

Research output: Contribution to journalArticle

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