Hardy E, Glenn J, Heptinstall S, Rubin P C, Horn E H
Department of Medicine, Queens Medical Centre, Nottingham, UK.
Thromb Haemost. 1995 Oct;74(4):1132-7.
This study has investigated the interaction of raised extracellular magnesium and agents which act via cAMP with respect to inhibition of platelet aggregation and effects on platelet cAMP accumulation. Iloprost (3 ng/ml) and PGD2 (0.2 microgram/ml) each caused time dependent increases in platelet cAMP which were significantly greater in the presence of 3 mM added MgSO4 (p < 0.01). Addition of ADP (5 microM) resulted in a fall in cAMP which remained higher in the presence of MgSO4 (p < 0.01). Forskolin (5 micrograms/ml) and DN9693 (100 microM) also caused increments in platelet cAMP but these responses were not influenced by added MgSO4. Addition of ADP resulted in a further increase in cAMP which was augmented by MgSO4 (p < 0.03). This increase was abolished by adenosine deaminase (1.2 U/ml). These experiments show that MgSO4 can modify the cAMP responses produced by iloprost and PGD2 and by forskolin and DN9693 when ADP is present. It appears that as well as inhibiting, ADP can also stimulate cAMP production under certain experimental conditions. This appears to be due to breakdown of ADP to adenosine.
本研究调查了细胞外镁升高与通过环磷酸腺苷(cAMP)起作用的药物在抑制血小板聚集及对血小板cAMP积累影响方面的相互作用。依洛前列素(3 ng/ml)和前列腺素D2(PGD2,0.2微克/ml)均可使血小板cAMP随时间增加,在添加3 mM硫酸镁的情况下,这种增加显著更大(p < 0.01)。添加二磷酸腺苷(ADP,5 microM)导致cAMP下降,但在硫酸镁存在时仍较高(p < 0.01)。福斯高林(5微克/ml)和DN9693(100 microM)也可使血小板cAMP增加,但这些反应不受添加的硫酸镁影响。添加ADP导致cAMP进一步增加,硫酸镁使其增强(p < 0.03)。这种增加被腺苷脱氨酶(1.2 U/ml)消除。这些实验表明,当存在ADP时,硫酸镁可改变依洛前列素、PGD2以及福斯高林和DN9693所产生的cAMP反应。似乎ADP除了具有抑制作用外,在某些实验条件下还可刺激cAMP生成。这似乎是由于ADP分解为腺苷所致。