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Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface


Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes1. Although there is little evidence to suggest that these processes are heterogeneous in platelets, we previously found that platelets co-stimulated with collagen and thrombin express functional α-granule factor V only on a subpopulation of cells2. Here we show that these cells, referred to as ‘COAT-platelets’, bind additional α-granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and α2-antiplasmin. These proteins are all transglutaminase substrates, and inhibitors of transglutaminase prevent the production of COAT-platelets. A synthetic transglutaminase substrate (CP15) also binds to COAT-platelets, and analysis by high performance liquid chromatography/mass spectrometry shows that a product is formed with a relative molecular mass (Mr) equal to CP15 plus 176. Serotonin, an abundant component of platelet-dense granules3, has an Mr of 176, and fibrinogen isolated from COAT-platelets contains covalently linked serotonin. Synthetic bovine serum albumin-(serotonin)6 binds selectively to COAT-platelets and also inhibits the retention of procoagulant proteins on COAT-platelets. These data indicate that COAT-platelets use serotonin conjugation to augment the retention of procoagulant proteins on their cell surface through an as yet unidentified serotonin receptor.

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Figure 1: α-Granule proteins are concentrated on the surface of COAT-platelets.
Figure 2: Dansylcadaverine, acetyl-casein and anti-FXIII inhibit COAT-platelet production.
Figure 3: Serotonin conjugation to CP15 and fibrinogen.
Figure 4: Binding of biotin-BSA-(5-HT)6 to activated platelets.
Figure 5: COAT-platelets bind low levels of PAC-1.


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This work was supported in part by an NIH grant (G.L.D.), the W.K. Warren Medical Research Institute (G.L.D.), Novartis (L.A) and the Swiss National Science Foundation (K.J.C.).

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Correspondence to George L. Dale.

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Dale, G., Friese, P., Batar, P. et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature 415, 175–179 (2002).

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