title: The effect of glycoprotein IIb-IIIa receptor occupancy on the cytoskeleton of resting and activated platelets.
abstract: The platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa), serves as the receptor for fibrinogen. This study examined what effect GPIIb-IIIa receptor occupancy had on the cytoskeleton of resting and activated platelets. Triton X-100-insoluble residues (cytoskeletons) were isolated from resting washed platelets incubated with either 500 microM RGDS or 500 microM RGES and examined for protein content. RGDS did not increase the amount of GPIIb-IIIa associated with the cytoskeletal residues which sedimented at either 15,800 x g or 100,000 x g. To determine the effect of receptor occupancy on the formation of the activated platelet cytoskeleton, stirred and nonstirred RGDS-treated platelets in plasma were activated with ADP. Triton X-100-insoluble residues were isolated and examined for both protein content and retention of GPIIb-IIIa. Further, morphological studies were performed on the RGDS-ADP-stimulated platelets. The results of this study suggest that 1) RGDS peptide receptor occupancy does not lead to GPIIb-IIIa linkage to the cytoskeleton, 2) ADP-stimulated platelet shape change, polymerization of actin, and association of myosin with the cytoskeleton are unaffected by RGDS peptide receptor occupancy. 3) RGDS inhibits an aggregation-dependent incorporation of ABP, alpha-actinin, talin, and GPIIb-IIIa into the Triton-insoluble residue.
authors.affiliation: Department of Medicine, University of Tennessee, Memphis 38163.
authors.forename: W C
authors.initials: WC
authors.lastname: Kouns
authors.forename: C F
authors.initials: CF
authors.lastname: Fox
authors.forename: W J
authors.initials: WJ
authors.lastname: Lamoreaux
authors.forename: L B
authors.initials: LB
authors.lastname: Coons
authors.forename: L K
authors.initials: LK
authors.lastname: Jennings
mesh_terms: D000185:Actinin / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D003571:Cytochalasin B / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D066298:In Vitro Techniques; D008840:Microfilament Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D016608:Talin
chemical_list: D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D016608:Talin; D000185:Actinin; D003571:Cytochalasin B; D000244:Adenosine Diphosphate; C046617:arginyl-glycyl-aspartyl-serine