Type

Journal Article

Authors

D Kenny
D C Shields
N Moran
G Meade
K Martin

Subjects

Pharmacology

Topics
platelet glycoprotein gpib ix complex platelet activation palmitic acid perfusion blood platelets pharmacokinetics humans pharmacology metabolism drug interactions physiology peptide fragments cytology drug effects von willebrand factor cell membrane permeability platelet aggregation inhibitors

A palmitylated peptide derived from the glycoprotein Ib beta cytoplasmic tail inhibits platelet activation. (2003)

Abstract The platelet receptor GPIb/IX/V mediates a crucial role in hemostasis, yet the signaling mechanisms involved are incompletely understood. The complex consists of four polypeptides GPIb alpha, GPIb beta, GPIX and GPV. We identified an amino acid sequence in the cytoplasmic tail of the GPIb beta subunit between residues R151 and A161 that is highly conserved across species and hypothesized that it has functional importance. To target this motif, we synthesized a corresponding cell-permeable palmitylated peptide (Pal-RRLRARARARA) and investigated its effect on platelet function. Pal-RRLRARARARA completely inhibited low dose thrombin- and ristocetin-induced aggregation in washed platelets but only partially inhibited collagen- and U46619-induced aggregation. Thromboxane production in platelets stimulated with thrombin was significantly reduced by Pal-RRLRARARARA compared with collagen. Activation of the integrin alpha IIb beta 3 in response to thrombin was significantly reduced when platelets were preincubated with Pal-RRLRARARARA. The adhesion of washed platelets to von Willebrand factor (VWF) under static conditions was significantly reduced by Pal-RRLRARARARA. Under conditions of high shear, the velocity of platelets rolling on VWF was significantly increased when platelets are preincubated with Pal-RRLRARARARA. This study defines a novel function for the RRLRARARARA motif of GPIb beta in platelet activation.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

D Kenny, D C Shields, N Moran, G Meade, K Martin

Experts in our system

1
Dermot Kenny
Royal College of Surgeons in Ireland
 
2
Denis C. Shields
University College Dublin
Total Publications: 123
 
3
Niamh Moran
Royal College of Surgeons in Ireland
Total Publications: 50
 
4
Gerardene Meade
Dublin City University
Total Publications: 13