摘要：Fluid-dynamic conditions that are compatible with tensile stress on the bonds between platelet
glycoprotein Ibα and immobilized von Willebrand factor A1 domain (VWF-A1) led to Ca++ release
from intracellular stores (type α/β peaks), which preceded stationary platelet adhesion. Raised levels
of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate inhibited these
[Ca++]i oscillations and prevented stable adhesion. Once adhesion was established through the integrin
αIIbβ3, new [Ca++]i oscillations (type γ) of greater amplitude and duration, and involving a transmembrane
ion flux, developed in association with the recruitment of additional platelets into aggregates.
We have defined the distinct roles that the two ADP receptors, P2Y1 and P2Y12, play in the early events
that follow the initial platelet interaction with immobilized VWF-A1 under high flow conditions. We
have examined the consequences of specific pharmacologic inhibition of P2 receptors and our findings
demonstrate a differential role of P2Y1 and P2Y12, respectively, in platelet adhesion and aggregation
onto immobilized VWF under elevated shear stress, and highlight the distinct contribution of signaling
pathways dependent on Src family kinases, PLC, and phosphoinositide 3-kinase (PI 3-K) to these
processes. Results have been achieved through original experiments under flow, thoroughly characterized
by ad hoc image analysis techniques and quantitative kinetic analysis.
