ADP-induced inhibition of von Willebrand factor-mediated platelet agglutination.
Human plasma von Willebrand factor (vWF) plus the antibiotic ristocetin, or bovine or porcine vWF alone, agglutinates platelets in either normal human ethylenediaminetetraacetate (EDTA)-treated citrated platelet-rich plasma (PRP) or citrated PRP from patients with the congenital platelet defect thrombasthenia. The prior addition of 1-10 muM ADP, which causes platelet shape change but not aggregation under these conditions, inhibited vWF-mediated agglutination. Inhibition was prevented by 200 muM ATP. Addition of ADP caused prompt reversal of established vWF-mediated agglutination, which resumed when the ADP was enzymatically removed. EDTA-treated, Formalin-fixed, washed normal platelets also underwent vWF-mediated agglutination. ADP was inhibitory only when added before fixation. Epinephrine (40 muM), prostaglandin E1 (7 muM), or serotonin (2 muM) added before fixation caused slight to moderate inhibition but always less than ADP. Platelets from blood chilled before fixation were fully active. Platelets fixed in freshly prepared PRP did not agglutinate as well as those fixed after incubation of PRP, probably because centrifugation exposes the platelets to ADP. It concluded that ADP causes a reversible decrease in the accessibility of the membrane receptor to vWF.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology; D003864:Depression, Chemical; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D007292:Inosine Nucleotides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D012310:Ristocetin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000502:physiology*
D001779:Blood Coagulation Factors; D006150:Guanine Nucleotides; D007292:Inosine Nucleotides; D011458:Prostaglandins E; D014841:von Willebrand Factor; D012310:Ristocetin; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004837:Epinephrine