Inhibition of Human Platelet Aggregation by Gangliosides

• Published in: Thrombosis research 2000-04, Vol.98 (1), p.51-57
• Main Authors: Guglielmone, Hugo A, Daniele, José J, Bianco, Ismael D, Fernandez, Eduardo J, Fidelio, Gerardo D
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - physiology; Cattle; Collagen - metabolism; Fundamental and applied biological sciences. Psychology; Gangliosides; Gangliosides - pharmacology; Humans; Molecular and cellular biology; Phospholipases; Platelet; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Signal transduction; Vasoconstrictor Agents - pharmacology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(99)00208-X

The content and composition of gangliosides is modified upon platelet stimulation, suggesting that these lipids may play functional roles in platelet physiology. Therefore, the effect of exogenously added gangliosides on human platelet aggregation was evaluated. The pretreatment of platelets with a mixture of total gangliosides from bovine brain and a series of purified mono-, di- and tri-sialogangliosides partially inhibit the collagen-induced aggregation process and ATP release and completely block the generation of the second aggregation wave when ADP is used as agonist. The inhibition was exerted at around 100 μM by G TOT as well as purified G M1, G M3, G D1a, and G T1b gangliosides, whereas asialoG M1 and sulphatide did not show a significant influence on platelet aggregation. Thrombin, Ca 2+ ionophores (A23187 and Ionomycin), arachidonic acid, and U46619 were unable to bypass the inhibitory effect exerted by gangliosides, suggesting that gangliosides inhibit platelet aggregation by inhibiting the synthesis or action of prostaglandins. Gangliosides inhibited U46619-induced aggregation, thus suggesting that they block the action of thromboxane A 2. Epinephrine induces a partial aggregation on gangliosides-treated platelets, similar to fluoroaluminate and phorbol myristate acetate, indicating that these platelets are still functional. To summarize, these results indicate that the major pathway(s), but not all, driving to the aggregation process following the interaction of ligand-receptor may be blocked by pretreatment of human platelets with gangliosides.