AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 1-H7, Copyright © 1985 by American Physiological Society
Thromboxane A2/prostaglandin H2 mobilizes calcium in human blood platelets
L. D. Brace, D. L. Venton and G. C. Le Breton
The present study investigated the mechanism by which thromboxane
A2/prostaglandin H2 (TXA2/PGH2) stimulates platelet activation. Previous
studies in isolated platelet vesicles have suggested that TXA2/PGH2
functions to release calcium from intraplatelet stores. On this basis, we
investigated whether TXA2/PGH2 causes mobilization of calcium in intact
platelets. Calcium redistribution was measured using the fluorescent probe,
chlortetracycline (CTC), and a photon-counting microspectrofluorometer.
Human platelet-rich plasma was incubated with CTC (50 microM) for 40 min at
25 degrees C. Shape change was induced with arachidonic acid (AA, 100
microM) or ADP (0.75-1.0 microM). It was found that AA addition resulted in
a significant release of intraplatelet calcium. This release was blocked by
inhibition of the cyclooxygenase with indomethacin (20 microM) or the
specific TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA, 100 microM).
On the other hand, neither indomethacin nor 13-APA had any effect on
calcium release stimulated by ADP. However, prostacyclin (13 nM) inhibited
both AA- and ADP-induced calcium release. These findings provide evidence
that cyclooxygenase products of AA, i.e., TXA2 and/or PGH2 directly caused
the mobilization of intraplatelet calcium. Furthermore, this calcium
mobilization appears to be mediated through a specific TXA2/PGH2 receptor
interaction.
