Effects of calmodulin inhibitors on rabbit synoviocyte phospholipase A2.
The effect of calmodulin inhibitors on synoviocyte phospholipase A2 activity was evaluated. Cells were incubated with [3H]arachidonic acid after 24 hours to label phospholipids. [3H]prostaglandin E2 synthesis was stimulated by Salmonella minnesota lipopolysaccharide (100 micrograms/ml). Trifluoperazine, 35 microM, reduced lipopolysaccharide-stimulated [3H]prostaglandin E2 synthesis by 50%. In sonicated suspensions of cells, calcium-dependent phospholipase A2 activity was inhibited by trifluoperazine 3-100 microM and by compound 48/80 (3 micrograms/ml). These agents inhibit calmodulin-dependent enzyme activity. The addition of calmodulin, 1 or 2.5 microM, to compound 48/80-treated suspensions reversed this inhibition in a dose-dependent manner. Agents which inhibit calmodulin-dependent enzymes can reversibly inhibit synoviocyte phospholipase A2 and thus prostaglandin E2 production.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D012475:Salmonella; D013583:Synovial Membrane / Q000201:enzymology*; D014268:Trifluoperazine / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001095:Arachidonic Acids; D002147:Calmodulin; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D014268:Trifluoperazine; D016718:Arachidonic Acid; D003189:p-Methoxy-N-methylphenethylamine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone