cGMP-independent inhibition of integrin αIIbβ3-mediated platelet adhesion and outside-in signalling by nitric oxide

AbstractWe examined the influence of S-nitrosoglutathione (GSNO) on αIIbβ3 integrin-mediated platelet adhesion to immobilised fibrinogen. GSNO induced a time- and concentration-dependent inhibition of platelet adhesion. Inhibition was cGMP-independent and associated with both reduced platelet spreading and protein tyrosine phosphorylation. To investigate the cGMP-independent effects of NO we evaluated integrin β3 phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of β3 on tyrosines 773 and 785, which was reduced by GSNO in a cGMP independent manner. Similar results were observed in suspended platelets indicating that NO-induced effects were independent of spreading-induced signalling. This is the first demonstration that NO directly regulates integrin β3 phosphorylation