Mechanisms involved in the antiplatelet activity of magnesium in human platelets
Mechanisms involved in the antiplatelet activity of magnesium in human platelets
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DOI：
10.1046/j.1365-2141.2002.03967.x
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发表时间：
2002-12-01
影响因子：
6.5
通讯作者：
Chou, DS
中科院分区：
文献类型：
--
作者：
Sheu, JR;Hsiao, G;Chou, DS
在这项研究中，硫酸镁剂量依赖性（0.6-3.0 mmol/l）抑制人血小板中由激动剂刺激的血小板聚集。此外，硫酸镁（3.0 mmol/l）显着干扰荧光素异硫氰酸酯-triflavin的糖蛋白（GP）IIb/IIIa复合物在血小板胶原蛋白刺激的结合。硫酸镁（1.5和3.0 mmol/l）也抑制磷脂酰肌醇的分解和细胞内Ca+2动员的人血小板胶原蛋白刺激。硫酸镁（3.0 mmol/l）可显著抑制血小板中胶原刺激的血栓素A（2）的形成。硫酸镁（1.5和3.0 mmol/l）可明显增强标记血小板膜的荧光。此外，硫酸镁（1.5和3.0 mmol/l）增加了血小板中环磷酸腺苷（AMP）的形成。硫酸镁（1.5 mmol/l）可显著抑制Mr 47 000（P47）蛋白的磷酸化。因此，硫酸镁的抗血小板活性可能涉及以下两个途径。(1)硫酸镁最初可诱导膜流动性改变，导致纤维蛋白原与GPIIb/IIIa复合物结合受到干扰，随后抑制磷酸肌醇分解和血栓素A（2）形成，从而抑制细胞内Ca 2+动员和P47磷酸化。(2)硫酸镁还可能触发环AM的形成，最终导致P47磷酸化和细胞内Ca+2动员的抑制。
In this study, magnesium sulphate dose-dependently (0.6-3.0 mmol/l) inhibited platelet aggregation in human platelets stimulated by agonists. Furthermore, magnesium sulphate(3.0 mmol/l) markedly interfered with the binding of fluorescein isothiocanate-triflavin to the glycoprotein (GP)IIb/IIIa complex in platelets stimulated by collagen. Magnesium sulphate (1.5 and 3.0 mmol/l) also inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. Magnesium sulphate (3.0 mmol/l) significantly inhibited thromboxane A(2) formation stimulated by collagen in platelets. Moreover, magnesium sulphate (1.5 and 3.0 mmol/l) obviously increased the fluorescence of platelet membranes tagged with diphenylhexatriene. In addition, magnesium sulphate (1.5 and 3.0 mmol/l) increased the formation of cyclic adenosine monophosphate (AMP) in platelets. Phosphorylation of a protein of Mr 47 000 (P47) was markedly inhibited by magnesium sulphate (1.5 mmol/l). In conclusion, the antiplatelet activity of magnesium sulphate may involve the following two pathways. (1) Magnesium sulphate may initially induce membrane fluidity changes with resulting interference of fibrinogen binding to the GPIIb/IIIa complex, followed by inhibition of phosphoinositide breakdown and thromboxane A(2) formation, thereby leading to inhibition of both intracellular Ca2+ mobilization and phosphorylation of P47. (2) Magnesium sulphate might also trigger the formation of cyclic AM, ultimately resulting in inhibition of the phosphorylation of P47 and intracellular Ca+2 mobilization.