Effect of berbamine on cytosolic phospholipase A(2) activation in rabbit platelets

The effect of berbamine, a biscoclaurine alkaloid, on cytosolic phospholipase A(2) activation in rabbit platelets was investigated. Berbamine inhibited iachidonic acid liberation induced by thrombin but not that by ionomycin. The alkaloid did not affect thrombin-stimulated Ca2+ mobilization, Ca2+-dependent translocation of cytosolic phospholipase A(2) to membranes, or the activity of partially purified cytosolic phospholipase A(2). Furthermore, berbamine had no effect an the thrombin-elicited increase in cytosolic phospholipase A(2) activity. However, berbamine suppressed arachidonic acid liberation in platelets stimulated with GTP-binding protein activators. Although incubation of platelet membranes with a GTP analogue decreased the islet-activating protein-catalyzed ADP-ribosylation of an approximately 40 kDa protein in the membranes, pretreatment of the membranes with berbamine did not influence the decrease in ADP-ribosylation, These results suggest that berbamine may impair GTP-binding protein-mediated activation of cytosolic phospholipase A(2), probably without influencing the enzyme translocation to membranes or the increase in the enzyme activity, and thus may cause the suppression of thrombin-induced arachidonic acid liberation.