TY - JOUR
T1 - Effect of picotamide on the calcium mobilization and phospholipase C activation in human platelets
AU - Pulcinelli, Fabio M.
AU - Pignatelli, Pasquale
AU - Riondino, Silvia
AU - Parisi, Simona
AU - Castiglioni, Carlo
AU - Gazzaniga, Pier Paolo
PY - 1994/6/1
Y1 - 1994/6/1
N2 - The effect of picotamide (G137 or N,N′-bis-3-picolyl-4-methoxy-isophthalamide), a dual thromboxane A2 (TxA2) synthetase inhibitor/TxA2 endoperoxide receptor antagonist, on the phospholipase C (PLC) activation and calcium mobilization in human platelets stimulated by arachidonic acid (AA) and TxA2 receptor synthetic agonist U46619, has been studied. Preincubation with picotamide (10-4 M) for 1 and 3 min significantly reduced (ps) by U46619 125 nM and 250 nM. Picotamide also reduced the calcium concentration changes induced in GFPs by AA 75 and 150 μM and by ADP 5 and 10 μM. In thrombin degranulated platelets picotamide inhibited the effect of U46619 up to 500 nM. The PLC activation, as indicated by inositol-1,3,4 P3 (Ins 1,3,4 P3) formation in response to U46619 250 nM and AA 150 μM was also inhibited by picotamide. These results may suggest a dual effect of picotamide on the receptor/effector systems through which TxA2 mediates platelet activation.
AB - The effect of picotamide (G137 or N,N′-bis-3-picolyl-4-methoxy-isophthalamide), a dual thromboxane A2 (TxA2) synthetase inhibitor/TxA2 endoperoxide receptor antagonist, on the phospholipase C (PLC) activation and calcium mobilization in human platelets stimulated by arachidonic acid (AA) and TxA2 receptor synthetic agonist U46619, has been studied. Preincubation with picotamide (10-4 M) for 1 and 3 min significantly reduced (ps) by U46619 125 nM and 250 nM. Picotamide also reduced the calcium concentration changes induced in GFPs by AA 75 and 150 μM and by ADP 5 and 10 μM. In thrombin degranulated platelets picotamide inhibited the effect of U46619 up to 500 nM. The PLC activation, as indicated by inositol-1,3,4 P3 (Ins 1,3,4 P3) formation in response to U46619 250 nM and AA 150 μM was also inhibited by picotamide. These results may suggest a dual effect of picotamide on the receptor/effector systems through which TxA2 mediates platelet activation.
KW - Antiplatelet drugs
KW - Phospholipase C
KW - Picotamide
KW - TxA receptor
UR - http://www.scopus.com/inward/record.url?scp=0028238192&partnerID=8YFLogxK
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U2 - 10.1016/0049-3848(94)90266-6
DO - 10.1016/0049-3848(94)90266-6
M3 - Article
C2 - 8085246
AN - SCOPUS:0028238192
VL - 74
SP - 453
EP - 461
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 5
ER -