[1-14C]Arachidonic acid incorporation into glycerolipids and prostaglandin synthesis in peritoneal macrophages: effect of chloramphenicol.
Peritoneal macrophages from normal mice were labelled with [1-14C]arachidonic acid after 2 h culture. The uptake of arachidonic acid into cellular lipids was rapid, time-dependent and can be represented within the limit of the studied times by a parabolic regression. Indomethacin decreased the kinetics of uptake; this inhibition is dose-dependent. Chloramphenicol had no effect on macrophage [1-14C]arachidonic acid uptake. After 3 h, the radioactivity was recovered in phosphatidylcholine (38.6%), phosphatidylserine-phosphatidylinositol (8.5%), phosphatidylethanolamine (22.1%), diacylglycerol (2.9%), triacyglycerol (2%) and cholesteryl ester (11.8%). Chloramphenicol and indomethacin inhibited the labelling of phospholipids and stimulated the labelling of neutral lipids and cholesteryl ester. Studies on arachidonic acid release from glycerolipids of prelabelled 2-h cultured macrophages showed that phosphatidylcholine and phosphatidylserine-phosphatidylinositol are the major source of arachidonic acid in prostaglandin synthesis in macrophages stimulated or not by zymosan. Chloramphenicol inhibited release of fatty acid from phosphatidylcholine and phosphatidylserine-phosphatidylinositol; indomethacin had no effect. Both drugs inhibited prostaglandin synthesis in stimulated or non-stimulated macrophages. In the culture medium, indomethacin increased the release of free arachidonic acid by stimulated macrophages. Possible explanations for the mechanisms underlying these effects are presented. It is concluded that indomethacin and chloramphenicol exert profound effects on the metabolism of phospholipids and its zymosan activation. Chloramphenicol appears to impair prostaglandin synthesis through several mechanisms and especially through phospholipase inhibition.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002701:Chloramphenicol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism*; D015054:Zymosan / Q000378:metabolism
D001095:Arachidonic Acids; D008563:Membrane Lipids; D011453:Prostaglandins; D016718:Arachidonic Acid; D002701:Chloramphenicol; D015054:Zymosan; D007213:Indomethacin