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, nordihydroguaiaretic acid and phenidone, blocked LTB4 synthesis without affecting ATP production. In conclusion, rat peritoneal leukocyte leukotriene synthesis depends on intact energy metabolism.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000037:antagonists & inhibitors; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010529:Peritoneal Cavity; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*
D001095:Arachidonic Acids; D013189:SRS-A; D016718:Arachidonic Acid; D000001:Calcimycin; D000255:Adenosine Triphosphate