Sphingosine 1-Phosphate Induces Platelet Activation through an Extracellular Action and Shares a Platelet Surface Receptor with Lysophosphatidic Acid

• Published in: The Journal of biological chemistry Vol. 272; no. 8; pp. 5291 - 5297
• Main Authors: Yatomi, Y, Yamamura, S, Ruan, F, Igarashi, Y
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 21.02.1997
• Subjects: Blood Platelets - metabolism; Calcium - metabolism; Humans; Lysophospholipids - metabolism; Platelet Activation; Receptors, Cell Surface - metabolism; Signal Transduction; Sphingosine - analogs & derivatives; Sphingosine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.8.5291

Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. We investigated the metabolism of Sph-1-P and the mechanism by which Sph-1-P induces activation in enucleated and highly differentiated platelets. Platelets lack Sph-1-P lyase activity, possess persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P. Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P, formed from exogenously added Sph by cytosolic Sph kinase, failed to do so. To support the notion that exogenous Sph-1-P stimulates platelets from outside, contact of platelet surfaces with immobilized Sph-1-P covalently linked to glass particles resulted in platelet activation. Furthermore, we detected the specific binding sites for radiolabeled Sph-1-P on the platelet surface, suggesting extracellular effects of Sph-1-P on plasma membrane receptors. This specific Sph-1-P binding was inhibited not by other sphingolipids but by lysophosphatidic acid (LPA), and platelet aggregation response to LPA was specifically desensitized by prior addition of Sph-1-P. Finally, internally stored Sph-1-P is released extracellularly upon stimulation, and the release correlated well with protein kinase C activation in intact platelets. These results suggest that Sph-1-P acts not intracellularly but intercellularly, following discharge from activated platelets, and shares a platelet surface receptor with LPA.