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 for 24 hours to label phospholipids. [³H]prostaglandin E₂ synthesis was stimulated by $\text{Salmonella minnesota}$ lipopolysaccharide (100 μg/ml). Trifluoperazine, 35 μM, 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 pM and by compound $\text{48}\text{80}$ (3 μg/ml). These agents inhibit calmodulin-dependent enzyme activity. The addition of calmodulin, 1 or 2.5 μM, to compound $\text{48}\text{80}\text{-}\text{treated}$ 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.