title: Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid.
abstract: 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.
authors.affiliation: Wellcome Italia Research Laboratories, Pomezia, Rome.
authors.forename: E
authors.initials: E
authors.lastname: Tubaro
authors.forename: L
authors.initials: L
authors.lastname: Belogi
authors.forename: C
authors.initials: C
authors.lastname: Croce
authors.forename: G
authors.initials: G
authors.lastname: Cavallo
authors.forename: G
authors.initials: G
authors.lastname: Guida
authors.forename: G P
authors.initials: GP
authors.lastname: Borelli
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D002240:Carbohydrate Sequence; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
chemical_list: D005732:Gangliosides; D010975:Platelet Aggregation Inhibitors; C084337:WILD 20; D012701:Serotonin; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin