Studies on the effect of platelet inhibitors on platelet adhesion to collagen and collagen-induced human platelet activation.
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 micrograms/ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 microM) as well as indomethacin (10 microM). At higher concentrations of collagen (10-15 micrograms/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.
D003094:Collagen / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*
D014268:Trifluoperazine; D012701:Serotonin; D011732:Pyridoxal Phosphate; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D007213:Indomethacin