Abstract
Dynorphins (dyn) are a major class of endogenous opioid peptides that modulate the functions of immune cells. However, the effects of dyn on the immune functions of glial cells in the central nervous system (CNS) have not been well characterized. Because nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) produced by glial cells are involved in various physiopathological conditions in the CNS, this study examined the effects of dyn on the production of NO and TNF-α from mouse glial cells treated with lipopolysaccharide (LPS). LPS induced a concentration-dependent increase in the production of NO or TNF-α from the mouse primary mixed glia cultures. Ultralow concentrations (10−16-10−12 M) of dynorphin (dyn) A-(1–8) significantly inhibited the LPS-induced production of NO or TNF-α. The inhibitory effects of dyn A-(1–8) were not blocked by nor-binaltorphimine, a selective κ opioid receptor antagonist. U50-488H, a selective κ opioid receptor agonist, did not affect the LPS-induced production of NO or TNF-α. Ultralow concentrations (10−16-10−12 M) of des-[Tyr1]-dyn A-(2–17), a nonopioid analog that does not bind to κ opioid receptors, exhibited the same inhibitory effects as dyn A-(1–17) and dyn A-(1–8). These results suggest that dyn modulate the immune functions of microglia and/or astrocytes in the brain and these modulatory effects of dyn are not mediated by classical κ opioid receptors.
Footnotes
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Send reprint requests to: Dr. Ling-Yuan Kong, Neuropharmacology Section, Laboratory of Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD: F1-01, Research Triangle Park, NC 27709.
- Abbreviations:
- LPS
- lipopolysaccharide
- NO
- nitric oxide
- TNF-α
- tumor necrosis factor-α
- IL
- interleukin
- dyn
- dynorphin
- nor-BNI
- nor-binaltorphimine
- CNS
- central nervous system
- HIV
- human immunodeficiency virus
- iNOS
- inducible NO synthase
- Received June 5, 1996.
- Accepted September 24, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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