Effects of picotamide on the calcium mobilization and phospholipase C activation in human platelets.

The effect of picotamide (G137 or N,N'-bis-3-picolyl-4-methoxyisophthalamide), a dual thromboxane A(2) (TxA(2)) synthetase inhibitor/TxA(2) endoperoxide receptor antagonist, on the phospholipase C (PLC) activation and calcium mobilization in human platelets stimulated by arachidonic acid (AA) and TxA(2) receptor synthetic agonist U46619, has been studied. Preincubation with picotamide (10(-4) M) for 1 and 3 min significantly reduced (p<0.03 and p<0.005 respectively) the calcium concentration changes induced in gel-filtered platelets (GFP(s)) by U46619 125 nM and 250 nM. Picotamide also reduced the calcium concentration changes induced in GFP(s) by AA 75 and 150 mu M and by ADP 5 and 10 mu M. In thrombin degranulated platelets picotamide inhibited the effect of U46619 up to 500 nM. The PLC activation, as indicated by inositol-1,3,4 P-3 (Ins 1,3,4 P-3) formation in response to U46619 250 nM and AA 150 mu M was also inhibited by picotamide. These results may suggest a dual effect of picotamide on the receptor/effector systems through which TxA(2) mediates platelet activation.