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Activation of mu opioid receptors inhibits microglial cell chemotaxis
1Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, Minnesota, USA.
Abstract:
Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.
Insights
Opiate drugs, specifically the mu opioid receptor (MOR), can reduce brain inflammation by inhibiting microglial cell migration. This suggests MOR activation may have anti-inflammatory effects in the central nervous system.
Area of Science:
- Neuroimmunology
- Pharmacology
Background:
- Microglia are brain macrophages that migrate to inflammatory sites.
- Opiates are known to modulate macrophage functions.
Purpose of the Study:
- To investigate the expression and function of the mu opioid receptor (MOR) in microglia.
- To determine if MOR activation affects microglial cell migration.
Main Methods:
- Analysis of MOR mRNA in microglial cells using specific primer sets.
- Assessment of microglial cell chemotaxis inhibition by morphine and DAMGO in vitro.
- Pharmacological characterization using a selective MOR antagonist.
Main Results:
- Microglial cells constitutively express MOR mRNA, identical to brain tissue.
- Morphine potently inhibited microglial chemotaxis toward C5a (IC50 = 1 fM).
- DAMGO, a selective MOR ligand, also suppressed chemotaxis (IC50 = 1 nM), blocked by beta-funaltrexamine.
Conclusions:
- Constitutively expressed MOR in microglia inhibits their chemotaxis.
- MOR activation may play an anti-inflammatory role in the brain.