MECHANISM OF PROSTAGLANDIN E(2) RELEASE AND INCREASE IN PGH(2) PGE(2) ISOMERASE ACTIVITY BY PDGF - INVOLVEMENT OF NITRIC-OXIDE

We examined the possibility that the platelet-derived growth factor-induced release of prostaglandin E(2) and increase in prostaglandin H-2 (PGHP)/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). (C) 1984 Academic Press, Inc.