ACTIVATION OF MU-OPIOID RECEPTORS INHIBITS MICROGLIAL CELL CHEMOTAXIS

Opiates modulate many macrophage functions. Microglia, the resident ma crophages of the brain, migrate to sites of inflammation within the CN S. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial ce lls 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 lig and, dose-dependently suppressed microglial cell chemotaxis with an IC 50 value of 1 nM, which was significantly attenuated by 10 nM beta-fun al-trexamine. Taken together, these findings suggest that activation o f constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the bra in.