Effects of calmodulin inhibitors on rabbit synoviocyte phospholipase A 2

Abstract

The effect of calmodulin inhibitors on synoviocyte phospholipase A 2 activity was evaluated. Cells were incubated with [ 3H]arachidonic acid for 24 hours to label phospholipids. [ 3H]prostaglandin E 2 synthesis was stimulated by Salmonella minnesota lipopolysaccharide (100 μg/ml). Trifluoperazine, 35 μM, reduced lipopolysaccharide-stimulated [ 3H]prostaglandin E 2 synthesis by 50%. In sonicated suspensions of cells, calcium-dependent phospholipase A 2 activity was inhibited by trifluoperazine 3–100 pM and by compound 48 80 (3 μg/ml). These agents inhibit calmodulin-dependent enzyme activity. The addition of calmodulin, 1 or 2.5 μM, 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 A 2 and thus prostaglandin E 2 production.