A POSSIBLE ROLE FOR PLATELET-ACTIVATING-FACTOR IN THE HYDROGEN PEROXIDE-INDUCED TXB(2), AND PGE(2) GLOMERULAR SYNTHESIS

Hydrogen peroxide stimulates both prostanoid and platelet-activating f actor (PAF) biosynthesis in cultured rat mesangial cells and isolated rat glomeruli. The present experiments were designed to try to establi sh some relationship between prostanoid and PAF synthesis in these ren al structures, in the presence of hydrogen peroxide. Cells and glomeru li were incubated with hydrogen peroxide under different experimental conditions, and thromboxane B-2 (TXB(2)), the stable metabolite of thr omboxane A(2) (TXA(2)), and prostaglandin E(2) (PGE(2)) concentrations were measured in the supernatants of the cells or glomeruli. Moreover , H2O2-dependent PAF synthesis was measured by high performance liquid chromatography (HPLC) ([H-3]acetate incorporation) and radioimmunoass ay. H2O2 induced increased TXB(2) and PGE(2) production in cultured ra t mesangial cells and isolated rat glomeruli. This effect was blocked by incubation in the presence of a PAF-receptor antagonist, BN-52021. This antagonist has no intrinsic effect either in basal prostanoid syn thesis or in arachidonic acid-stimulated glomerular TXB(2) synthesis. Alprazolam, another PAF antagonist, nonchemically related to BN-52021, also completely blocked the H2O2-induced production of TXB(2) by isol ated rat glomeruli. Moreover, H2O2 was also able to induce an increase d [H-3]acetate incorporation into a fraction comigrating with a PAF st andard in HPLC in isolated glomeruli, and this effect was dependent on the H,Oz concentration tested. Moreover, H2O2 was also able to induce an increased [H-3]acetate incorporation and increased synthesis of ra dioimmunoassayable PAF in cultured mesangial cells. These results sugg est that the increased synthesis of PGE(2) and TXB(2) induced by H2O2 could be dependent on platelet-activating factor production.