Effects of ATP on ligand recognition of platelet fibrinogen receptor on GPIIb-IIIa

M. P. Gawaz, P. Mayinger, F. J. Neumann

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The recent discovery of 8-azido-ATP binding sites on the platelet fibrinogen receptor glycoprotein complex GPIIb-IIIa suggests that extracellular ATP may directly modulate function of GPIIb-IIIa. In this study we investigated the effect of ATP on ligand binding to GPIIb-IIIa. Fibrinogen-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) used to induce platelet activation. In addition, 8-azido-ATP and ATP inhibited binding of 125I-labeled fibrinogen to thrombin- and phorbol ester-activated platelets. Interaction of nonstimulated platelets with solid-phase fibrinogen was also reduced by 8-azido-ATP and ATP. Moreover, fibrinogen mimetic peptide-induced conformational change of GPIIb-IIIa on resting platelets was reduced in the presence of both nucleotides. Finally, photoincorporation of 8-azido-[γ-32P]ATP into GPIIb-IIIa was suppressed by GRGDSP but not by the biologically inactive GRGESP peptide. Thus interaction of ATP with 8-azido- ATP binding sites present on GPIIb-IIIa modulate receptor function, which may play a role in regulation of in vivo platelet aggregation.

Original languageEnglish (US)
Pages (from-to)H1098-H1106
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number3 36-3
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • extracellular adenosine 5'- triphosphate
  • photoaffinity labeling
  • platelet aggregation
  • thrombosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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