Objective: To evaluate the anti-thrombotic action of glucosamine, a naturally occurring amino monosaccharide, platelets were stimulated with ADP in the presence of glucosamine, and its effects on platelet functions were examined.
Materials and methods: Human platelet-rich plasma was stimulated with 2.5 microM ADP in the presence of glucosamine (0.01 approximately 1 mM) or other aminosugars (N-acetyl-glucosamine, galactosamine or N-acetyl-galactosamine, 1 mM), and platelet aggregation was monitored. Furthermore, the effects of glucosamine on the thromboxane A2 production, release of granule contents, intracellular calcium mobilization and phosphorylation of Syk (a 72 kD protein tyrosine kinase) were evaluated following ADP-stimulation. In addition, the binding of [3H] ADP to its receptors was examined.
Results: Glucosamine (>0.01 mM) dose-dependently suppressed platelet aggregation in response to ADP (p < 0.05), whereas N-acetyl-glucosamine, galactosamine or N-acetyl-galactosamine (1 mM) did not affect the ADP-induced platelet aggregation. Furthermore, glucosamine (>0.1 mM) inhibited the extracellular release of granule contents (ATP and platelet factor 4) and production of thromboxane A2 from ADP-stimulated platelets (p < 0.05). Moreover, glucosamine significantly repressed the intracellular calcium mobilization at >0.1 mM and phosphorylation of Syk at >0.01 mM upon ADP-stimulation (p < 0.05). In addition, glucosamine (>0.1 mM) inhibited the binding of ADP to its receptors (p < 0.05).
Conclusion: Glucosamine is able to suppress platelet aggregation, release of granule constituents, thromboxane A2 production, calcium mobilization and phosphorylation of Syk possibly via the inhibition of ADP-binding to the receptors. Glucosamine could be expected as a novel anti-platelet agent for thrombotic disorders due to its suppressive actions on platelets.