Unexpected effects of aurin tricarboxylic acid on human platelets.
Aurin tricarboxylic acid (ATA) is a potent inhibitor of ristocetin-mediated platelet agglutination and of shear-induced, von Willebrand factor (vWf)-mediated platelet aggregation, probably via inhibition of vWf interaction with glycoprotein Ib (GPIb). We examined the effects of ATA (both the sodium salt and a solution of ATA in ethanol) on platelet functions in citrated plasma (PRP) and in suspensions of washed platelets in Tyrode-albumin solution (contains 2 mM Ca2+). ATA (42-211 micrograms/ml) blocked aggregation and release of granule contents induced by thrombin (0.15 U/ml in PRP; 0.03 U/ml in platelet suspension). Responses to higher concentrations of thrombin were not inhibited. ATA also prolonged thrombin-induced clotting of fibrinogen. Since ATA had no effect on fibrinogen-induced responses of chymotrypsin-treated platelets, ATA probably acts on thrombin rather than on fibrinogen. In PRP and platelet suspensions, ATA (acid form 106 micrograms/ml; sodium salt 122 micrograms/ml) had little effect on ADP-induced platelet aggregation. The sodium salt of ATA (61-122 micrograms/ml) enhanced collagen-induced aggregation and release by platelets in citrated plasma and by washed platelets; the enhancement was extensively inhibited by aspirin. With platelet suspensions, ATA significantly enhanced aggregation and release caused by low concentrations of sodium arachidonate (15-50 microM); aggregation and release caused by higher concentrations of arachidonate were somewhat inhibited by ATA. Arachidonate-induced aggregation and release were also enhanced by ATA in PRP. ATA enhanced aggregation and release induced by the calcium ionophore A23187; aspirin had little effect on the enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinlough-Rathbone
R L
RL
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Packham
M A
MA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012310:Ristocetin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D012310:Ristocetin; D016718:Arachidonic Acid; D012701:Serotonin; D000001:Calcimycin; D001312:Aurintricarboxylic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin