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.