Exclusive expression of the Gs-linked prostaglandin E2 receptor subtype 4 mRNA in mononuclear Jurkat and KM-3 cells and coexpression of subtype 4 and 2 mRNA in U-937 cells.
Prostaglandin E2 (PGE2) is regarded as a potent regulator of the immune system. It can regulate apoptosis in mononuclear cells and modulate the cytokine secretion pattern from T-helper cell subpopulations via an increase in cyclic AMP (cAMP). Of the 4 PGE2 receptor subtypes (EP1-EP4) that are defined pharmacologically by their affinity to subtype-specific ligands and their coupling to G proteins, EP2 and EP4 receptors couple to Gs. It is as yet unknown which of these two receptor subtypes mediates the immunomodulatory effects. By quantitative RT-PCR, the mRNA for EP4 receptors was demonstrated and quantified in the human mononuclear cell lines Jurkat, KM-3 and U-937. However, EP2 receptor mRNA was only present in U-937 cells and was 100-fold less abundant than EP4 receptor mRNA. PGE2 increased cAMP formation with an ED50 of 50-100 nM in all cell lines. cAMP formation was inhibited by the EP4R-specific antagonist AH23848. Since AH23848 inhibited PGE2-induced cAMP formation in U-937 cells to a similar extent as in Jurkat and KM-3, EP2 receptors seem to play, if any, only a secondary role for the PGE2-mediated cAMP formation in U-937 cells.
Blaschke
V
V
Institüt fur Biochemie und Molekulare Zellbiologie, Georg-August-Universität, Göttingen, Germany.
Jungermann
K
K
Püschel
G P
GP
D001713:Biphenyl Compounds / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D001713:Biphenyl Compounds; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; C046926:AH 23848; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D015232:Dinoprostone