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

Treatment with 100 mu M 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 mu M prostaglandin E-2 (PGE(2)). PCE2-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 mu M. The EP2 agonist butaprost also reduced ATP-induced migration at 10 mu M, whereas the EP1 agonist 17-phenyl trinor PGE(2), the EP3 agonist sulprostone, and the EP4 agonist PGE(1) alcohol all had no effect at 10 mu M. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 mu M, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE(2) on ATP-induced migration at 100 mu M. Over the same experimental duration, PGE(2), butaprost, and forskolin had little effect on cell viability. These findings indicate that ATP-induced microglial migration is reduced by PGE(2) through EP2 and adenylate cyclase. (C) 2008 Elsevier B.V. All rights reserved.