Convulxin-induced platelet aggregation is accompanied by a powerful activation of the phospholipase C pathway.
Platelet aggregation and stimulation of phosphoinositide-specific phospholipase C (PLC) by thrombin and by convulxin (Cvx), a non-enzymic snake venom glycoprotein, were compared. Cvx-stimulated production of inositol phosphates by washed platelets was independent of the cyclo-oxygenase pathway, formation of platelet-activating factor and ADP release, but prostacyclin (prostaglandin I2), a stimulator of cyclic AMP formation, suppressed its effects on platelet and PLC activation. Kinetic analysis showed that inositol 1,4,5-trisphosphate formation reached its maximal value 15 s after platelet stimulation with Cvx and persisted for at least 5 min. Neomycin sulphate (10 mM), which complexes phosphatidylinositol 4-phosphate and phosphatidyl-inositol 4,5-bisphosphate, decreased the production of inositol phosphates, partially prevented platelet aggregation induced by a high concentration of Cvx (10 nM) and abolished both platelet aggregation and inositol phosphate formation induced by thrombin (2 units/ml) and by a stable prostaglandin H2 analogue, U46619 (1 microM). In contrast with neomycin sulphate, Na2SO4 had no significant effect against all agonists tested. It is concluded that platelet activation by Cvx is partially mediated by PLC and involves other mechanisms as well.
Faili
A
A
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U285, Paris, France.
Randon
J
J
Francischetti
I M
IM
Vargaftig
B B
BB
Hatmi
M
M
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology*; D004347:Drug Interactions; D004789:Enzyme Activation; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D037181:Lectins, C-Type; D009355:Neomycin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D014230:Triazoles / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D001381:Azepines; D003435:Crotalid Venoms; D007295:Inositol Phosphates; D037181:Lectins, C-Type; D014230:Triazoles; C052518:WEB 2086; C028890:convulxin; D011464:Epoprostenol; D010738:Type C Phospholipases; D009355:Neomycin; D002118:Calcium