Mechanism of prostaglandin E2 release and increase in PGH2/PGE2 isomerase activity by PDGF: involvement of nitric oxide.
We examined the possibility that the platelet-derived growth factor-induced release of prostaglandin E2 and increase in prostaglandin H2 (PGH2)/prostaglandin E2 (PGE2) isomerase activity (EC 5.3.99.3) in NIH3T3 cells was mediated by nitric oxide. Addition of L-NG-nitroarginine methyl ester or diphenyleneiodonium chloride, potent nitric oxide synthase inhibitors, blocks platelet derived growth factor-induced release of prostaglandin E2, lowers basal prostaglandin E2 release, and also blocks the growth factor-induced increase in PGH2/PGE2 isomerase activity. Exogenous nitric oxide stimulates prostaglandin E2 release in NIH3T3 cells and this stimulation is blocked by hemoglobin. In contrast, exogenous nitric oxide failed to induce prostaglandin E2 release from pEJ/ras-transformed cells. The nitric oxide induction of PGH2/PGE2 isomerase activity and prostaglandin E2 release occurred within minutes in contrast to alterations in prostaglandin H synthase/cyclooxygenase. These findings link three different classes of messenger molecules (growth factors, nitric oxide, prostaglandins).
Kelner
M J
MJ
Department of Pathology, University of California, San Diego 92103-8302.
Uglik
S F
SF
D016475:3T3 Cells; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009861:Onium Compounds / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D015398:Signal Transduction
D000634:Aminoquinolines; D009861:Onium Compounds; D010982:Platelet-Derived Growth Factor; D009569:Nitric Oxide; C007517:diphenyleneiodonium; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester