Effect 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 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 (p < 0.03 and p < 0.005 respectively) the calcium concentration changes induced in gel-filtered platelets (GFPs) by U46619 125 nM and 250 nM. Picotamide also reduced the calcium concentration changes induced in GFPs by AA 75 and 150 microM and by ADP 5 and 10 microM. 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 microM 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.
Pulcinelli
F M
FM
Dept. of Experimental Medicine, University of Rome La Sapienza, Italy.
Pignatelli
P
P
Riondino
S
S
Parisi
S
S
Castiglioni
C
C
Gazzaniga
P P
PP
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002850:Chromatography, Gel; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D010795:Phthalic Acids / Q000494:pharmacology*; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000187:drug effects*
D010795:Phthalic Acids; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C011581:picotamide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010738:Type C Phospholipases; D013917:Thrombin; D001241:Aspirin; D002118:Calcium