Prostaglandin E2 reduces extracellular ATP-induced migration in cultured rat microglia

Treatment with 100 μM adenosine triphosphate (ATP) for 120 min augmented migration of cultured rat microglia by about 4-fold. This augmentation was effectively reduced by 0.1–10 μM prostaglandin E2 (PGE2). PGE2-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 μM. The EP2 agonist butaprost also reduced ATP-induced migration at 10 μM, whereas the EP1 agonist 17-phenyl trinor PGE2, the EP3 agonist sulprostone, and the EP4 agonist PGE1 alcohol all had no effect at 10 μM. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 μM, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE2 on ATP-induced migration at 100 μM. Over the same experimental duration, PGE2, butaprost, and forskolin had little effect on cell viability. These findings indicate that ATP-induced microglial migration is reduced by PGE2 through EP2 and adenylate cyclase.