Summary
The effect of pyridoxal 5’-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin
antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied
using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and
[14C]-5HT release induced by “threshold” or low concentrations of collagen (0.6 μg/ ml)
in PRP were completely abolished by PALP (24 mM), TFPZ (250 μM) as well as indomethacin
(10 μM). At higher concentrations of collagen (10–15 μg/ml) in PRP and WPL, the use
of stirred and unstirred platelets treated with collagen enabled a distinction to
be made between aggregation and adhesion- mediated release reaction. Platelet aggregation
and the aggregation-mediated release reaction induced by these concentrations of collagen
in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although
neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred
platelets was significantly affected by these inhibitors. Interestingly, both adhesion
and the adhesion-mediated release reaction were abolished by concentrations of PALP
10–40 fold higher than those required to abolish aggregation. Collagen-induced platelet
aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated
with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion.
The results further emphasize the distinction between adhesion and aggregation-mediated
events with regards to collagen with the latter being more susceptible to inhibition
by antiplatelet agents such as PALP and TFPZ.
Keywords
Platelet adhesion - Pyridoxal 5’-phosphate - Trifluoperazine
