Aluminium fluoride enhances phospholipase A2 activity and eicosanoid synthesis in macrophages.
Eicosanoid synthesis in macrophages is controlled by the availability of free arachidonic acid. Activation of the phospholipase A2 (PLA2) is an important mechanism leading to increased eicosanoid synthesis. In order to obtain further insight into the regulatory mechanisms of eicosanoid release, we incubated macrophages with the protein kinase C (PKC) activator dioctanoylglycerol (DiC8) or aluminium fluoride (AIF4-), a well-described activator of guanine nucleotide binding proteins (G-proteins). Arachidonic acid release, membrane-bound PLA2 activity and prostaglandin production in macrophages were enhanced by both substances in a time-dependent manner. Incubation with the phorbol ester TPA had no effect on the PLA2-activity. AIF4- elevated the cellular diacylglycerol content. The results suggest that activation of PLA2 and successive eicosanoid synthesis by AIF4- is mediated by direct activation of PLA2 by the AIF4(-)-induced generation of diacylglycerol.
Wessel
K
K
Department of Pharmacology and Toxicology, Medical School of Hannover, Federal Republic of Germany.
Resch
K
K
Kaever
V
V
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism
D017607:Aluminum Compounds; D004075:Diglycerides; D015777:Eicosanoids; C044295:1,2-dioctanoylglycerol; D000535:Aluminum; D011493:Protein Kinase C; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride