title: Inhibition of platelet adhesion to fibrin(ogen) in flowing whole blood by Arg-Gly-Asp and fibrinogen gamma-chain carboxy terminal peptides.
abstract: We have employed synthetic peptides with sequences corresponding to the integrin receptor-recognition regions of fibrinogen as inhibitors of platelet aggregation and adhesion to fibrinogen- and fibrin-coated surfaces in flowing whole blood, using a rectangular perfusion chamber at wall shear rates of 300 s-1 and 1,300 s-1. D-RGDW caused substantial inhibition of platelet aggregation and adhesion to fibrinogen and fibrin at both shear rates, although it was least effective at blocking platelet adhesion to fibrin at 300 s-1. RGDS was a weaker inhibitor, and produced a biphasic dose-response curve; SDRG was inactive. HHLGGAKQAGDV partially inhibited platelet aggregation and adhesion to fibrin(ogen) at both shear rates. These results support the identification of an RGD-specific receptor, most likely the platelet integrin glycoprotein IIb:IIIa, as the primary receptor responsible for platelet:fibrin(ogen) adhesive interactions under flow conditions, and indicate that platelet adhesion to surface bound fibrin(ogen) is stabilized by multivalent receptor-ligand contacts.
authors.affiliation: Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1016.
authors.forename: R R
authors.initials: RR
authors.lastname: Hantgan
authors.forename: S C
authors.initials: SC
authors.lastname: Endenburg
authors.forename: I
authors.initials: I
authors.lastname: Cavero
authors.forename: G
authors.initials: G
authors.lastname: Marguerie
authors.forename: A
authors.initials: A
authors.lastname: Uzan
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
mesh_terms: D000595:Amino Acid Sequence; D005337:Fibrin / Q000187:drug effects*; D005340:Fibrinogen / Q000187:drug effects*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D012697:Serine Endopeptidases / Q000378:metabolism; D012995:Solubility; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D014867:Water; C047981:arginyl-glycyl-aspartic acid; D005337:Fibrin; D005340:Fibrinogen; D012697:Serine Endopeptidases