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Inter‐individual variability in Ca 2+ signalling in platelets from healthy volunteers: effects of aspirin and relationship with expression of endomembrane Ca 2+ ‐ATPases
Author(s) -
Feijge Marion A. H.,
Van Pampus Elisabeth C. M.,
LacabaratzPorret Christine,
HamulyÀk Karly,
LévyToledano Sylviane,
Enouf Jocelyne,
Heemskerk Johan W. M.
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00844.x
Subject(s) - serca , thapsigargin , platelet , thrombin , thromboxane , endocrinology , medicine , chemistry , thromboxane a2 , atpase , endoplasmic reticulum , platelet activation , aspirin , biochemistry , enzyme
Increased Ca 2+ signal generation may lead to hyperactivity of platelets and contribute to thrombotic complications. Using fura‐2‐loaded platelets from 51 healthy volunteers, high variability was detected in the Ca 2+ responses evoked by the receptor agonists, thrombin and collagen, and the inhibitor of sarco/endoplasmic reticulum Ca 2+ ‐ATPases (SERCA), thapsigargin (Tg). Oral intake of 500 mg aspirin reduced the magnitude of the Ca 2+ responses, and lowered the intra‐individual coefficients of variance of the responses by 50%. However, the corresponding inter‐individual variance coefficients were only a little influenced by aspirin intake, pointing to subject‐dependent factors in Ca 2+ handling that are unrelated to thromboxane formation. With each agonist, 6–9% of the subjects had platelets with relatively high Ca 2+ responses (> mean + SD) both before and after aspirin intake. In 90% (9/10) of these cases the high responsiveness was confirmed in platelets obtained 6–12 months later. The Tg‐ but not thrombin‐induced Ca 2+ responses correlated inversely with the expression levels of SERCA PL/IM 430 (SERCA‐3b) in platelets. After aspirin intake, the Ca 2+ responses with collagen but not thrombin correlated inversely with SERCA‐2b expression. These results suggest that, in the absence of potentiating effects of thromboxane, (i) the amount of PL/IM 430‐recognizable SERCA may control the Ca 2+ signal when SERCA‐2b is specifically inhibited (with Tg), and (ii) the expression of SERCA‐2b determine the collagen‐ but not the thrombin‐evoked Ca 2+ signal. Accordingly, limited Ca 2+ ‐pumping activity by low expression of one of the SERCA isoforms is likely to be one of the factors resulting in increased platelet activity towards collagen or thapsigargin but not thrombin.