Mechanism of Prostaglandin E 2 Release and Increase in PGH 2 /PGE 2 Isomerase Activity by PDGF: Involvement of Nitric Oxide

• Published in: Archives of biochemistry and biophysics Vol. 312; no. 1; pp. 240 - 243
• Main Authors: Kelner, M.J., Uglik, S.F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 1994
• DOI: 10.1006/abbi.1994.1305
• ISSN: 0003-9861

We examined the possibility that the platelet-derived growth factor-induced release of prostaglandin E 2 and increase in prostaglandin H 2 (PGH 2)/prostaglandin E 2 (PGE 2) isomerase activity (EC 5.3.99.3) in NIH3T3 cells was mediated by nitric oxide. Addition of L- N G-nitroarginine methyl ester or diphenyleneiodonium chloride, potent nitric oxide synthase inhibitors, blocks platelet derived growth factor-induced release of prostaglandin E 2, lowers basal prostaglandin E 2 release, and also blocks the growth factor-induced increase in PGH 2/PGE 2 isomerase activity. Exogenous nitric oxide stimulates prostaglandin E 2 release in NIH3T3 cells and this stimulation is blocked by hemoglobin. In contrast, exogenous nitric oxide failed to induce prostaglandin E 2 release from pEJ/ ras-transformed cells. The nitric oxide induction of PGH 2/PGE 2 isomerase activity and prostaglandin E 2 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).