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 platelets [Y. Yatomi et al., Biochem. Biophys. Res. Commun. 231 (1997) 848-851]. In this study, we synthesized, for the first time, DMS-1-P and examined 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 sphingosine 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 [3H]Sph-1-P was performed using DMS-1-P. DMS-1-P reduced the binding of [3H]Sph-1-P to platelets almost as much as unlabeled 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.
Yatomi
Y
Y
Department of Laboratory Medicine, Yamanashi Medical University, Japan.
Yamamura
S
S
Ruan
F
F
Kume
S
S
Ozaki
Y
Y
Igarashi
Y
Y
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C105100:N,N-dimethylsphingosine-1-phosphate; D013110:Sphingosine