Influence of calcium on arachidonic acid mobilization by murine resident peritoneal macrophages.
Stimulation of resident peritoneal macrophages resulted in release of arachidonic acid (AA) from phospholipids. This AA release is believed to occur as a result of the activation of phospholipases, usually by a phospholipase A2 (PLA2). The purpose of this study was to elucidate the role of cytosolic calcium ion concentration ([Ca2+]i) in the modulation of [3H]AA mobilization in peritoneal macrophages. [3H]AA release induced by ionophore A23187, opsonized zymosan, or 4 beta-phorbol 12-myristate acetate (PMA) occurred in the absence of extracellular calcium. Studies in fura-2/AM-loaded cells showed that zymosan and PMA did not increase [Ca2+]i significantly, whereas A23187 induced PLA2 activity translocation up to plasmatic membrane. Thapsigargin, an inhibitor of endomembrane Ca(2+)-ATPase, induced a rise in [Ca2+]i when cells were incubated in a Ca2+ medium. However, thapsigargin was not an effective stimulator of the translocation of PLA2 activity and [3H]AA release. These data indicate that changes in [Ca2+]i were not sufficient to elicit [3H]AA mobilization; this process seems tightly modulated by phosphorylation-dependent mechanisms in the presence of low [Ca2+]i.
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007476:Ionophores; D013729:Terpenes; D016718:Arachidonic Acid; D000001:Calcimycin; D019284:Thapsigargin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium