RT Journal Article SR Electronic T1 Thromboxane A2/prostaglandin H2 directly stimulates platelet shape change independent of secreted ADP. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 276 OP 281 VO 222 IS 1 A1 L V Parise A1 D L Venton A1 G C Le Breton YR 1982 UL http://jpet.aspetjournals.org/content/222/1/276.abstract AB 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, 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. These findings provide evidence that the interaction of TXA2/PGH2 with its receptor results in the direct stimulation of shape change independent of secreted ADP. Furthermore, maintenance of this shape change response appears to require continued occupation of the TXA2/PGH2 receptor.