Glucosamine, a naturally occurring amino monosaccharide, suppresses the ADP-mediated platelet activation in humans.
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.


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).


CONCLUSIONS
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.
Hua
J
J
Department of Host Defense and Biochemical Research, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Suguro
S
S
Iwabuchi
K
K
Tsutsumi-Ishii
Y
Y
Sakamoto
K
K
Nagaoka
I
I
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000586:Amination; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D005944:Glucosamine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009005:Monosaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D000072377:Syk Kinase; D013928:Thromboxane A2 / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D009005:Monosaccharides; D018048:Receptors, Purinergic P2; D010978:Platelet Factor 4; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D005944:Glucosamine; D002118:Calcium