N,N-DIMETHYLSPHINGOSINE 1-PHOSPHATE ACTIVATES HUMAN PLATELETS

We recently reported that N,N-dimethylsphingosine 1-phosphate (DMS-1-P ) can be formed from N,N-dimethylsphingosine (DMS) in activated platel ets [Y. Yatomi et al., Biochem. Biophys. Res. Commun. 231 (1997) 848-8 51]. In this study, we synthesized, for the first time, DMS-1-P and ex amined the functional effects of DMS-1-P and its related sphingolipids on platelets, Although exogenous DMS was inactive, Its phosphorylated derivative, DMS-1-P, induced platelet intracellular Ca2+ mobilization and shape change, but not aggregation or release reactions, Since sph ingosine 1-phosphate (Sph-1-P) is structurally related to DMS-1-P and activates platelets more strongly than DMS-1-P, a competitive binding experiment for [H-3]Sph-1-P was performed using DMS-1-P. DMS-1-P reduc ed the binding of [H-3]Sph-1-P to platelets almost as much as unlabele d Sph-1-P did, These results suggest that DMS-1-P activates platelets via an interaction with a platelet surface receptor for Sph-1-P. (C) 1 997 Federation of European Biochemical Societies.