A major role of ADP in thromboxane transfer experiments: studies in patients with platelet secretion defects.
Because of its unstable nature, previous studies of the effect of thromboxane A2 on platelets have been performed by incubating normal platelets with arachidonic acid (generating system) and transferring aliquots of platelet suspensions or their supernates containing thromboxane A2 to indomethacin-treated platelets (recipient system). These studies concluded that thromboxane A2 could induce irreversible aggregation of and 14C-serotonin secretion from the recipient platelets. Our studies indicate that ADP plays a major role in the responses induced by such transferred aliquots in recipient platelets, and that the effects previously attributed solely to thromboxane A2 occur because of a synergism between thromboxane A2 and ADP, which consists of ADP transferred passively and ADP secreted by the recipient platelets. We found optimum dense granule secretion to be dependent on the presence of an intact cyclooxygenase pathway in the recipient platelets and on close cell contact, suggesting that thromboxane A2 may not be as strong an agonist (direct inducer of secretion) as generally considered. Several investigators have performed similar transfer experiments using platelets from patients with secretion defects despite normal granule contents. On the basis of diminished response in the patients' platelets to aliquots of normal platelets stimulated with arachidonic acid, they concluded that the defective platelet secretion was caused by an impaired response to thromboxane A2. Because of the role of ADP demonstrated, we caution against such an inference regarding responsiveness of platelets to thromboxane A2 based purely on the results of the transfer experiments.
D000244:Adenosine Diphosphate / Q000097:blood / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D013928:Thromboxane A2 / Q000097:blood / Q000502:physiology*; D013931:Thromboxanes / Q000502:physiology*
D001095:Arachidonic Acids; D013931:Thromboxanes; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate