Sphingosine 1-phosphate induces platelet activation through an extracellular action and shares a platelet surface receptor with lysophosphatidic acid.
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.
Yatomi
Y
Y
The Biomembrane Institute, Seattle, Washington 98119, USA.
Yamamura
S
S
Ruan
F
F
Igarashi
Y
Y
D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D015539:Platelet Activation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D008246:Lysophospholipids; D011956:Receptors, Cell Surface; C060506:sphingosine 1-phosphate; D013110:Sphingosine; D002118:Calcium