title: Occupancy of glycoprotein IIb/IIIa by B-6 vitamers inhibits human platelet aggregation.
abstract: Vitamin B-6 inhibits platelet aggregation. However, the effect of the occupancy of GPIIb/IIIa, a major receptor responsible for aggregation on platelet membranes, by B-6 vitamers on platelet aggregation is unknown. This study was carried out to quantify GPIIb/IIIa occupancy in platelets treated with B-6 vitamers [pyridoxal-5-phosphate (PLP); pyridoxal (PL); pyridoxine (PN); pyridoxamine (PM)], using a monoclonal antibody-based assay, by flow cytometry. Antibody binding was compared with inhibition of platelet aggregation. PLP, PL, PN and PM occupied GPIIb/IIIa with dissociation constants of 1.83 +/- 1.15, 19.43 +/- 7.86, 3.63 +/- 1.67 and 10.89 +/- 2.93 mmol/L, respectively. Occupancy of GPIIb/IIIa by the four B-6 vitamers was negatively correlated with platelet aggregation (r = -0.90 to -0.94, P < 0.001). The concentrations of the four B-6 vitamers that inhibited maximal platelet aggregation were in the order of PLP < PN <PM < PL, the same order in which they occupied > or =80% of the GPII/IIIa receptor. Platelet aggregation was inhibited by B-6 vitamers via the occupancy of GPIIb/IIIa with the potency of PLP > PN > PM > PL.
authors.affiliation: Department of Biology, National Cheng Kung University, Tainan, Taiwan. sjchang@mail.ncku.edu.tw
authors.forename: S-J
authors.initials: SJ
authors.lastname: Chang
authors.forename: C-N
authors.initials: CN
authors.lastname: Chang
authors.forename: C-W
authors.initials: CW
authors.lastname: Chen
mesh_terms: D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008024:Ligands; D010974:Platelet Aggregation; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism*; D011485:Protein Binding; D025101:Vitamin B 6 / Q000378:metabolism*
chemical_list: D039661:Integrin beta3; D008024:Ligands; D040201:Platelet Membrane Glycoprotein IIb; D025101:Vitamin B 6