title: cGMP-independent inhibition of integrin alphaIIbbeta3-mediated platelet adhesion and outside-in signalling by nitric oxide.
abstract: We examined the influence of S-nitrosoglutathione (GSNO) on alpha(IIb)beta(3) 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 beta(3) phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of beta(3) 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 beta(3) phosphorylation.
authors: Centre for Atherothrombosis Research, Department of Medical Biosciences, University of Bradford, Richmond Building, Richmond Road, Bradford, West Yorkshire BD7 1DP, UK.
authors: Nikolaus G
authors: NG
authors: Oberprieler
authors: Wayne
authors: W
authors: Roberts
authors: Rocio
authors: R
authors: Riba
authors: Anne M
authors: AM
authors: Graham
authors: Shervanthi
authors: S
authors: Homer-Vanniasinkam
authors: Khalid M
authors: KM
authors: Naseem
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010766:Phosphorylation; D010973:Platelet Adhesiveness / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D020030:Nitric Oxide Donors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D009569:Nitric Oxide; D014443:Tyrosine; D026422:S-Nitrosoglutathione; D005340:Fibrinogen; D006152:Cyclic GMP