THROMBOXANE A2 PROSTAGLANDIN H-2 DIRECTLY STIMULATES PLATELET SHAPE CHANGE INDEPENDENT OF SECRETED ADP

  • 1 January 1982
    • journal article
    • research article
    • Vol. 222  (1) , 276-281
Abstract
The relative contribution of thromboxane (TX)A2/prostaglandin (PG)H2 and ADP to platelet shape change was determined using the specific TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA) and the ADP antagonist, ATP. Shape change was induced in human platelet-rich plasma with doses of arachidonic acid (AA) or the PG endoperoxide analog U46619 [15 (S)-hydroxy-11.alpha.,9.alpha.-(epoxymethano)prosta-5Z,13E-dienoic acid], which did not cause measurable ATP/ADP release. Pretreatment of platelet-rich plasma with 13-APA completely inhibited shape change to AA or U46619 but did not inhibit ADP-induced shape change. In contrast, ATP completely blocked shape change to ADP but not to AA or U46619. In addition, 13-APA and ATP also selectively reversed shape change. Thus, 13-APA added 1.5 min subsequent to AA or U46619 resulted in almost complete reversal of the shape change response. However, 13-APA did not reverse ADP-induced shape change. A similar selectivity was observed with ATP which reversed shape change to ADP but not to AA or U46619. The interaction of TXA2/PGH2 with its receptor results in the direct stimulation of shape change independent of secreted ADP. Maintenance of this shape change response appears to require continued occupation of the TXA2/PGH2 receptor.