LEUKOTRIENE PRODUCTION IN RAT PERITONEAL LEUKOCYTES REQUIRES INTACT ENERGY-METABOLISM

Compounds which inhibit cellular production of ATP either by uncoupling of oxidative phosphorylation (valinomycin, carbonylcyanide-4-trifluoromethoxphenylhydrazone, and 2,4-dinitrophenol), glycolytic phosphorylation (2-deoxy-D-glucose) or by inhibiting respiratory-chain reactions (antimycin A) were all shown to inhibit calcium-ionophore A23187-induced leukotriene synthesis in rat peritoneal leukocytes at concentrations closely correlating with those needed to block ATP synthesis. In contrast, none of the compounds interfered with cyclo-oxygenase or other enzymes involved in arachidonate metabolism in these cells. Two well-known inhibitors of 5-lipoxygenase, nordihydroguaiarctic acid and phenidone, blocked LTB4 synthesis without affecting ATP production. In conclusion, rat peritoneal leukocyte leukotriene synthesis depends on intact energy metabolism.