[Effects of SIN-1, a metabolite of molsidomine, on paf-acether-blood platelets interactions].
The metabolite of molsidomine, 3-morpholino-syndnonimine (SIN-1) is a vasodilator and an inhibitor of platelet activation induced by adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin. We present the results of SIN-1 on platelet aggregation induced by paf-acether and on the biosynthesis of this mediator by washed rabbit platelets. SIN-1 inhibits submaximal platelet aggregation induced by 50 pM paf-acether. This inhibition is dose-dependent (SIN-1 IC50: 37 +/- 10 nM, n = 3). SIN-1 also inhibits submaximal aggregations induced by ADP (IC50: 13 +/- 11 nM) and AA (IC50: 26 +/- 12 nM) (n = 3-5). Finally, SIN-1 inhibits dose-dependently the formation of lyso paf-acether (the precursor of paf-acether) and of thromboxane A2, and AA freeing by thrombin-stimulated platelets. Thus SIN-1 has a wide spectrum activity on platelets. He is both capable of inhibiting platelet aggregation induced by all used agonists and to inhibit the formation of paf-acether and thromboxane A2, two powerful mediators of platelet aggregation.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism
D010972:Platelet Activating Factor; D013928:Thromboxane A2; C002385:linsidomine; D008981:Molsidomine
Effets du SIN-1, le métabolite de la molsidomine, sur les interactions paf-acéther plaquettes.