Platelet GPIb-V-IX Complex

Abstract

The GPIb-V-IX complex forms one of the major adhesion receptors on the platelet surface and has a vital role in primary haemostasis as an essential link between ttreplatelet and von Willebrand factor (vWO, associated with collagen on damaged vessel wall. Although there are still a number of problems to be solved concerning the activation of the binding site on GPIb for vWf by shear sfress and the role of the various subunits in signal transmission, there is now sufficient basic knowledge about the structure of the complex and the signals ttrat are induced to provide a basic theory of how it functions. Platelet activation by vWf has much in common with two other agonists, collagen and aggregated IgG, all of which stimulate an early, intense, tyrosine phosphorylation response and it has long been suspected that they use common mechanisms involving platelet Fc receptors and clustering of specific receptors via these multimeric ligands. The GPIb-V-IX/vWf axis presents an attractive alternative to GPllbllla#ibrinogen as a target for platelet inhibition since suitable inhibitors might be expected to down regulate other manifestations of platelet activity such as granule releoso, ttrought to play a role in the development of arteriosclerosis. Substances which could be used as a basis for such inhibitors have been identified in snake venoms and ttreir mode of action is currently under investigation.