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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 gamma, tumor necrosis factor alpha, and interleukin-1beta, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), on cytokine induced iNOS expression in human astroglia. beta-FNA dose-dependently inhibited iNOS expression. beta-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 beta-FNA may provide insights for pharmacologic strategies to treat or prevent brain pathologies associated with neuroinflammation.


Randall L Davis, Daniel J Buck, Neda Saffarian, Shekher Mohan, Udaya DeSilva, Samodha C Fernando, Craig W Stevens. Beta-funaltrexamine inhibits inducible nitric-oxide synthase expression in human astroglial cells. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2008 Sep;3(3):150-3

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PMID: 18278557

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