Summary
Trifluoperazine (TFP) in concentrations up to 10-15 μM increased the formation of
phosphatidic acid (PA) in platelets treated with 0.5 U/ml of thrombin, while higher
concentrations of TFP inhibited formation of PA. Liberation of arachidonate (AA) from
platelet phospholipids was progressively inhibited as the concentration of TFP increased.
At thrombin doses lower than 0.1 U/ml TFP, (≤25 μM) enhanced PA formation with either
no effect on AA liberation (6 donors) or with much greater enhancement of PA formation
than the decrease in liberation of AA (3 donors). The enhancement of PA formation
by TFP did therefore not seem to be due to inhibition of phospholipase A2 (PLA2) by the phenothiazine, which has been suggested. We show further that TFP inhibits
PA phosphohydrolase in platelet lysates, although with complex kinetics. It is therefore
concluded that the enhancement of thrombin-induced PA production by TFP is not caused
by inhibition of PLA2 but could be due to TFP-induced inhibition of PA phosphohydrolase.
