Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid

• Published in: European journal of pharmacology Vol. 248; no. 2; pp. 175 - 183
• Main Authors: Tubaro, E, Belogi, L, Croce, C, Cavallo, G, Guida, G, Borelli, G P
• Format: Journal Article
• Language: English
• Published: Netherlands 02.08.1993
• Subjects: Animals; Bleeding Time; Blood Platelets - drug effects; Carbohydrate Sequence; Dose-Response Relationship, Drug; Gangliosides - pharmacology; Male; Mice; Molecular Sequence Data; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Rabbits; Rats; Rats, Wistar; Serotonin - blood; Thrombin - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0926-6917(93)90040-W

Gal beta 1-->3GalN beta 1-->4Gal(3<--2 alpha Neu)beta 1-->4Glc beta-->1Sph (WILD20), a new glycosphingolipid, a breakdown product of the monosialoganglioside GM1 obtained through alkaline hydrolysis, shows dose-dependent platelet anti-aggregating properties in vitro and in vivo. This effect is agonist- and species-independent. The family of lysosphingolipids, to which the compound belongs, is present in platelets particularly after thrombin treatment. WILD20 antiplatelet effect is due to the interference with ADP or thrombin-induced aggregation, probably via phospholipase A2 (PLA2) blockade; the substance is also effective when arachidonic acid is used as an agonist. Serotonin blood levels are also reduced. The substance, orally active at dosages of 0.1-0.01 mg/kg as antiplatelets agent, prolonged bleeding time without interfering with the coagulative or fibrinolytic processes.