Calcium mobilization in human platelets by receptor agonists and calcium‐ATPase inhibitors

FEBS Letters

Ullrich, Volker¹  Brüne, Bernhard¹ 

[1] Faculty of Biology, University of Konstanz, Germany

关键词: Human platelet;    Calcium pool;    Thapsigargin;    2;    5-Di(tert-butyl)-1;    4-benzohydroquinone;    [Ca2+]i;    intracellular calcium;    tBuBHQ;    2;    5-di(tert-butyl)-1;    4-benzohydroquinone;    TG;    thapsigargin;    U46619;    15S-hydroxy-11;    9-[epoxymethano]prosta-5;    13-dienoic acid;   

DOI  :  10.1016/0014-5793(91)80747-Q

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Inhibitors of the endoplasmic reticulum Ca²⁺-ATPase like thapsigargin (TG) and 2,5-di (tert-butyl)-1,4-benzohydroquinone (tBuBHQ) cause increases in cytosolic calcium in intact human platelets resulting from prevention of reuptake. A maximal concentration of TG (0.2 μM) mobilized 100% of sequestered Ca²⁺ compared to the action of a receptor agonist like thrombin (0.1 U/ml). A maximal dose of tBuBHQ (50 μM) stimulated release of about 40% of intracellular calcium compared to thrombin and TG. The reduced ability of tBuBHQ to release calcium can be explained with an inhibitory effect on the cyclooxygenase pathway (K _i ≈ 7 μM). Thererore tBuBHQ is not able to cause platelet aggregation compared to TG. In the presence of a cyclooxygenase inhibitor or a thromboxane A₂ receptor antagonist the action of TG is identical to that observed with tBuBHQ. Generally, inhibition of calcium sequestration does not automatically result in platelet activation. In contrast to a receptor mediated activation Ca²⁺-ATPase inhibitors require the self-amplification mechanism of endogenously formed thromboxane A₂ to cause a similar response. We conclude that the calcium store sensitive to Ca²⁺-ATPase inhibitors is a subset of the receptor sensitive calcium pool.

【 授权许可】

Unknown