Ca2+ influx and platelet membrane glycoproteins.
When aequorin-loaded platelets were stimulated with thrombin, the luminescence of aequorin showed two peaks. From experiments with 1 mM external Ca2+ or 1 mM EGTA, both one-half of the first peak and the entire second peak reflected the influx of Ca2+ from the external medium, and the remaining half of the first peak reflected the mobilization of Ca2+ from its storage site. A monoclonal antibody (TM83), that recognizes the GPIIb/IIIa complex which has binding sites for fibrinogen, and synthetic peptide GRGDSP are known to inhibit fibrinogen binding and platelet aggregation. Both of them eliminated the second peak of intracellular free calcium. Similar effects were observed during activation by collagen, but not by TPA. Also dihydrocytochalasin B inhibited the second peak of Ca2+ influx by thrombin, suggesting that the signal, which was caused by fibrinogen-binding to GPIIb/IIIa (aggregation) in thrombin-activated platelets, is transferred to the inner sites of GPIIb/IIIa complex and induces the cytoskeletal reorganization such as actin polymerization. This in turn, induces the secondary increase in [Ca2+] i of platelets. It is interesting that ticlopidine inhibited the Ca2+ influx through the GPIIb/IIIa complex. This result suggests the importance of such kinds of antiplatelet drugs to prevent thrombus formation.
Yamaguchi
A
A
Tanoue
K
K
Yamazaki
H
H
D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*
D010980:Platelet Membrane Glycoproteins; D002118:Calcium