Differential effect of SIN-1 on thromboxane and prostacyclin formation in platelets and endothelial cells.
The effect of SIN-1, the active metabolite of molsidomine that inhibits platelet aggregation, was tested upon the oxidation of arachidonic acid in platelets and endothelial cells. The metabolism of arachidonic acid from both exogenous and endogenous sources was investigated by determining the formation of thromboxane and prostacyclin. These prostanoids were measured in platelets and endothelial cells alone or during their interaction, in the absence or presence of SIN-1. The presence of endothelial cells decreased the generation of thromboxane by the platelets, especially from endogenous arachidonate, whereas the platelets tended to increase that of prostacyclin under basal conditions. SIN-1 significantly reduced the production by the platelets of metabolites from endogenous arachidonic acid but did not affect those from exogenous sources. The reduction in metabolism of endogenous arachidonate was more pronounced in the presence of endothelial cells. In contrast, SIN-1 did not alter the production of cyclo-oxygenase metabolites of arachidonic acid in endothelial cells. Thus, the liberation of arachidonic acid, leading to prostanoid synthesis, may be regulated differentially in platelets and endothelial cells: molsidomine might be a potential antithrombogenic drug because it alters specifically the phospholipase activity in the platelets.
Lagarde
M
M
INSERM U205, Chimie Biologique INSA, Villeurbanne, France.
Bordet
J C
JC
Croset
M
M
D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010101:Oxygen Consumption; D013931:Thromboxanes / Q000096:biosynthesis*; D014471:Umbilical Veins; D014665:Vasodilator Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D013931:Thromboxanes; D014665:Vasodilator Agents; C002385:linsidomine; D008981:Molsidomine; D011464:Epoprostenol