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Calcium mobilization in human platelets by receptor agonists and calcium‐ATPase inhibitors
Author(s) -
Brüne Bernhard,
Ullrich Volker
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80747-q
Subject(s) - thapsigargin , chemistry , calcium , serca , endocrinology , medicine , receptor , calcium atpase , thromboxane a2 , thromboxane , platelet , agonist , thrombin , calcium in biology , thromboxane receptor , atpase , biochemistry , biology , enzyme , organic chemistry
Inhibitors of the endoplasmic reticulum Ca 2+ ‐ATPase like thapsigargin (TG) and 2,5‐di ( tert ‐butyl)‐1,4‐benzohydroquinone ( t BuBHQ) 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 Ca 2+ compared to the action of a receptor agonist like thrombin (0.1 U/ml). A maximal dose of t BuBHQ (50 μM) stimulated release of about 40% of intracellular calcium compared to thrombin and TG. The reduced ability of t BuBHQ to release calcium can be explained with an inhibitory effect on the cyclooxygenase pathway ( K i ≈ 7 μM). Thererore t BuBHQ is not able to cause platelet aggregation compared to TG. In the presence of a cyclooxygenase inhibitor or a thromboxane A 2 receptor antagonist the action of TG is identical to that observed with t BuBHQ. Generally, inhibition of calcium sequestration does not automatically result in platelet activation. In contrast to a receptor mediated activation Ca 2+ ‐ATPase inhibitors require the self‐amplification mechanism of endogenously formed thromboxane A 2 to cause a similar response. We conclude that the calcium store sensitive to Ca 2+ ‐ATPase inhibitors is a subset of the receptor sensitive calcium pool.