Stimulation of phospholipase activity and prostaglandin biosynthesis by melittin in cell culture and in vivo

Melittin, a membrane-active peptide of bee venom, as well as synthetic melittin, stimulated the biosynthesis of prostaglandins by mouse transformed fibroblasts (MC5-5), human fibroblasts (D550), rabbit aorta endothelial cells (CLO), rat lung type II alveolar pneumocytes (L-2) and rabbit smooth muscle cells (R-I). The melittin peptides also stimulated the release of arachidonic acid from the cellular Phospholipids of MC5-5 cells. The stimulated prostaglandin biosynthesis by MC5-5 cells was inhibited by indomethacin and dexamethasone. Dexamethasone inhibited also the release of arachidonic acid by MC5-5 cells. In mice, intraperitoneal inoculation of melittin increased 13,14-dihydro-15-keto-PGE2 levels in peripheral blood. Prior injections of the mice with indomethacin prevented the melittin-induced increase in this PGE2 metabolite.