Cox D, Seki J
Centre for Cardiovascular Science, Royal College of Surgeons, Dublin, Ireland.
Thromb Res. 1998 Aug 1;91(3):129-36. doi: 10.1016/s0049-3848(98)00080-2.
125I-fibrinogen bound to ADP-activated fixed platelets in a saturable manner. The Scatchard plot was curvilinear but nonlinear model fitting of the data suggested that there was only one binding site with KA=4.19+/-1.3 x 10(6) M(-1) and a maximum number of binding sites of 3.9+/-1.1 x 10(4) molecules/platelet. The GPIIb/IIIa antagonists RGDS and FK633 both inhibited 125I-fibrinogen binding (50 microg/ml) in a dose-dependent manner. FK633 had a KB value of 2.5+/-0.48 x 10(7) M(-1) (Kb=39.9 nM) and an IC50, value of 64 nM, while RGDS had an KB of 2.55+/-0.76 x 10(4) M(-1) (Kb=39.2 microM) with an IC50 value of 63 microM. At concentrations below its IC50 value FK633 was a competitive antagonist of fibrinogen binding. However, at concentrations above its IC50 value it was a noncompetitive antagonist. The IC50 values of FK633 remained constant over a wide range of fibrinogen concentrations while its KB value changed-increasing from 1.8+/-0.6 x 10(7) M(-1) at 10 microg/ml 125I-fibrinogen to 4.5+/-1.6 x 10(7) M(-1) at 300 microg/ml and decreasing to 0.3+/-0.2 x 10(7) M(-1) at 2.4 mg/ml. Thus, FK633 is a reversible, noncompetitive antagonist of fibrinogen binding to the platelet GPIIb/IIIa receptor.
125I-纤维蛋白原以可饱和的方式与二磷酸腺苷激活的固定血小板结合。Scatchard图呈曲线状，但对数据进行非线性模型拟合表明，只有一个结合位点，解离常数KA = 4.19±1.3×10(6) M(-1)，每个血小板结合位点的最大数量为3.9±1.1×10(4)个分子。糖蛋白IIb/IIIa拮抗剂RGDS和FK633均以剂量依赖的方式抑制125I-纤维蛋白原的结合（50微克/毫升）。FK633的平衡解离常数KB值为2.5±0.48×10(7) M(-1)（Kb = 39.9纳摩尔），半数抑制浓度IC50值为64纳摩尔，而RGDS的KB值为2.55±0.76×10(4) M(-1)（Kb = 39.2微摩尔），IC50值为63微摩尔。在低于其IC50值的浓度下，FK633是纤维蛋白原结合的竞争性拮抗剂。然而，在高于其IC50值的浓度下，它是非竞争性拮抗剂。在广泛的纤维蛋白原浓度范围内，FK633的IC50值保持恒定，而其KB值发生变化，从10微克/毫升125I-纤维蛋白原时的1.8±0.6×10(7) M(-1)增加到300微克/毫升时的4.5±1.6×10(7) M(-1)，并在2.4毫克/毫升时降至0.3±0.2×10(7) M(-1)。因此，FK633是纤维蛋白原与血小板糖蛋白IIb/IIIa受体结合的可逆性非竞争性拮抗剂。
