Original article: Effects of Raised Extracellular Magnesium on Platelet Reactivity.
The inhibitory effects on platelet reactivity of increased extracellular magnesium were investigated. Wherever possible, experiments were performed in hirudinized whole blood. Concentration dependent inhibition of platelet aggregation and dense granule release were observed with MgSO(4). Antiaggregatory effects were identical with MgCl(2), indicating that the effects are due to the Mg(2+) ion. Antiaggregatory effects of CaCl(2), differed from those of MgCl(2), indicating that this is not a non-specific divalent cation effect. MgSO(4) also caused concentration-dependent inhibition of platelet thromboxane production. Experiments in the presence of apyrase and indomethacin showed that complex formation with ADP and inhibition of cyclo-oxygenase do not entirely account for the inhibitory effect of magnesium on platelet activation. Studies with an anti-GPIIb/IIIa antibody showed that the inhibitory effects on the release reaction and thromboxane synthesis are independent of those on aggregation. The results are consistent with magnesium modifying an intracellular signal transduction pathway common to several agonists, rather than the effects of magnesium being specific for one agonist. This study also shows that MgSO(4) inhibits agonist-induced increases in intracellular free calcium. Increasing the extracellular concentration of magnesium up to 10 mM had no effect on agonist-induced increments in intraplatelet free Mg(2+) concentration.
S. Heptinstall, P. C. Rubin, E. H. Horn, Department of Medicine, Queens Medical Centre, Nottingham, NG7 2UH.
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Horn