Mechanisms involved in the antiplatelet activity of magnesium in human platelets.
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 A2 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 A2 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.
Sheu
Joen-Rong
JR
Graduate Institute of Medical Sciences and Department of Pharmacology, Taipei Medical University, Taipei, Taiwan. sheujr@tmu.edu.tw
Hsiao
George
G
Shen
Ming-Yi
MY
Fong
Tsorng-Harn
TH
Chen
Yi-Win
YW
Lin
Chien-Huang
CH
Chou
Duen-Suey
DS
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000097:blood; D018929:Cell Culture Techniques; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D010716:Phosphatidylinositols / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D010716:Phosphatidylinositols; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013929:Thromboxane B2; D008278:Magnesium Sulfate; D003094:Collagen; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium