Prostaglandin E2 reduces extracellular ATP-induced migration in cultured rat microglia.
Treatment with 100 microM 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 microM prostaglandin E(2) (PGE(2)). PGE(2)-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 microM. The EP2 agonist butaprost also reduced ATP-induced migration at 10 microM, 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 microM. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 microM, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE(2) on ATP-induced migration at 100 microM. 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.
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Takayuki
T
Nagano
Shinya H
SH
Kimura
Motohiko
M
Takemura
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype
D004791:Enzyme Inhibitors; C545646:Ptger2 protein, rat; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D005576:Colforsin; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone