Yatomi Y, Yamamura S, Ruan F, Kume S, Ozaki Y, Igarashi Y
Department of Laboratory Medicine, Yamanashi Medical University, Japan.
FEBS Lett. 1997 Nov 17;417(3):341-4. doi: 10.1016/s0014-5793(97)01321-5.
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.
我们最近报道，在活化的血小板中，N,N-二甲基鞘氨醇1-磷酸酯（DMS-1-P）可由N,N-二甲基鞘氨醇（DMS）生成[Y. Yatomi等人，《生物化学与生物物理研究通讯》231（1997）848 - 851]。在本研究中，我们首次合成了DMS-1-P，并研究了DMS-1-P及其相关鞘脂对血小板的功能影响。尽管外源性DMS无活性，但其磷酸化衍生物DMS-1-P可诱导血小板细胞内Ca2+动员和形态改变，但不诱导聚集或释放反应。由于鞘氨醇1-磷酸酯（Sph-1-P）在结构上与DMS-1-P相关，且比DMS-1-P更强烈地激活血小板，因此使用DMS-1-P进行了[3H]Sph-1-P的竞争性结合实验。DMS-1-P对[3H]Sph-1-P与血小板结合的减少程度几乎与未标记的Sph-1-P相同。这些结果表明，DMS-1-P通过与血小板表面Sph-1-P受体相互作用来激活血小板。
