AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 8-13, Copyright © 1985 by American Physiological Society
Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets
L. D. Brace, D. L. Venton and G. C. Le Breton
We previously demonstrated that thromboxane A2 and/or prostaglandin H2
(TXA2/PGH2), ADP, and A23187 cause calcium mobilization in intact human
platelets. Other studies have also shown that platelet shape change and
aggregation induced by a variety of platelet agonists can be reversed by
specific antagonists. In the present study, we used the fluorescent calcium
probe chlortetracycline to evaluate whether the reversal of platelet
activation involves a resequestration of intraplatelet calcium. It was
found that the TXA2/PGH2 receptor antagonist 13-azaprostanoic acid (13-APA)
reversed calcium mobilization and shape change induced by AA but not that
induced by ADP. A similar specificity of action was observed using the
specific ADP receptor antagonist, ATP, in that ATP only reversed
ADP-induced calcium release and shape change. In contrast, prostacyclin
reversed both AA and ADP-induced calcium redistribution and shape change.
In the latter experiments, a net calcium sequestration was actually
observed on prostacyclin addition. These findings indicate that the
resequestration of released calcium leads to platelet deactivation.
Furthermore, there appear to be at least two mechanisms by which a
reduction in cytosolic calcium can be produced: specific interruption of
the agonist-receptor interaction, for example, 13-APA antagonism of
TXA2/PGH2; and stimulation of platelet adenosine 3',5'-cyclic monophosphate
production by prostacyclin and consequent calcium sequestration.
