EFFECTS OF ATP ON LIGAND RECOGNITION OF PLATELET FIBRINOGEN RECEPTOR ON GPIIB-IIIA

The recent discovery of 8-azido-ATP binding sites on the platelet fibr inogen receptor glycoprotein complex GPIIb-IIIa suggests that extracel lular ATP may directly modulate function of GPIIb-IIIa. In this study we investigated the effect of ATP on ligand binding to GPIIb-IIIa. Fib rinogen-mediated aggregation of washed platelets was inhibited by ATP and 8-azido-ATP in a dose-dependent manner, independent of the agonist (thrombin, collagen, epinephrine, phorbol 12-myristate 13-acetate) us ed to induce platelet activation. In addition, 8-azido-ATP and ATP inh ibited binding of I-125-labeled fibrinogen to thrombin- and phorbol es ter-activated platelets. Interaction of nonstimulated platelets with s olid-phase fibrinogen was also reduced by 8-azido-ATP and ATP. Moreove r, fibrinogen mimetic peptide-induced conformational change of GPIIb-I IIa on resting platelets was reduced in the presence of both nucleotid es. Finally, photoincorporation of 8-azido-[gamma-P-32]ATP into GPIIb- IIIa was suppressed by GRGDSP but not by the biologically inactive GRG ESP peptide. Thus interaction of ATP with 8-azido-ATP binding sites pr esent on GPIIb-IIIa modulate receptor function, which may play a role in regulation of in vivo platelet aggregation.