Morphine preconditioning reduces lipopolysaccharide and interferon-gamma-induced mouse microglial cell injury via delta 1 opioid receptor activation.
Microglial cells play an important role in the inflammatory response of a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to protect microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) induced cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released from the cells. Preconditioning the cells with morphine for 30 min concentration-dependently reduced LPS plus IFN gamma-induced cell injury. This morphine preconditioning effect was abolished by naloxone, a general opioid receptor antagonist, by naltrindole, a selective delta opioid receptor antagonist and by 7-benzylidenenaltrexone maleate, a selective delta(1) opioid receptor antagonist. However, this protective effect was not affected by beta-funaltrexamine, a selective mu opioid receptor antagonist, nor-binaltorphimine, a selective kappa opioid receptor antagonist or naltriben, a selective delta(2) opioid receptor antagonist. LPS plus IFN gamma induced the expression of inducible nitric oxide synthase (iNOS), which was not affected by morphine preconditioning. Our results suggest that morphine induced a preconditioning effect in microglial cells. This effect may be mediated by delta 1 opioid receptors and may not be through inhibiting the expression of iNOS, a potentially harmful protein.
Department of Anesthesiology, University of Virginia Health System, University of Virginia, 1 Hospital Drive, Charlottesville, VA 22908-0710, USA; Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.
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Gwak
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D000818:Animals; D002460:Cell Line; D007371:Interferon-gamma / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors
D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D009020:Morphine; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II