A combination of lactacystin and 12-O-tetradecanoylphorbol-13-acetate enhances the release of arachidonic acid from cells in cultures: release is reduced in confluent and serum deprived cells

Lactacystin, a selective inhibitor of some proteasome activities, in the pr esence of 12-tetradecanoyl phorbol-13-acetate stimulates the release of ara chidonic acid from the phospholipids of bovine pulmonary artery endothelial , bovine embryonic thoracic aorta smooth muscle, rat liver and rat glial ce lls. The enhanced release from rat liver cells is inhibited by dexamethason e, aspirin, Na salicylate and the immunosuppressive fungal metabolite, glio toxin. The effects of aspirin plus dexamethasone are not additive, but thos e of gliotoxin plus dexamethasone are additive. The stimulated and unstimul ated release from all four cells are decreased when these cells are grown t o confluence or when they are growth arrested by serum deprivation. The uns timulated as well as the stimulated release is partially inhibited by the c ytosolic phospholipase A(2) inhibitor, methylarachidonyl fluorophosphonate. The enhanced release is reduced in the presence of the translation and tra nscription inhibitors, actinomycin and cycloheximide. (C) 2000 Harcourt Pub lishers Ltd.