K. Nakamura et al., DUALITY OF PLASMIN EFFECT ON CYTOSOLIC-FREE CALCIUM IN HUMAN PLATELETS, American journal of physiology. Cell physiology, 37(4), 1995, pp. 958-967
Plasmin caused a modest and gradual increase in platelet cytosolic Ca2
+, mediated through both Ca2+ mobilization and external Ca2+ entry. Th
is response was associated with accelerated Ca2+ extrusion and protein
tyrosine phosphorylation. Plasmin-enhanced external Ca2+ entry and Ca
2+ extrusion (but not Ca2+ mobilization) were attenuated by the tyrosi
ne kinase inhibitor, genistein. Plasmin inhibited the thrombin-evoked
increase in cytosolic Ca2+ and also inhibited the Ca2+ response to the
tethered peptide TRAP-6 of the thrombin receptor. Furthermore, plasmi
n inhibited the binding of I-125-labeled alpha-thrombin to platelets.
The inhibitory effect of plasmin on the thrombin response shared some
characteristics with the effect of protein kinase C stimulators but wa
s not reversed by protein kinase C inhibitors. Plasmin did not change
platelet cyclic nucleotides. These results suggest a dual effect of pl
asmin. Plasmin produces a small rise in platelet cytosolic Ca2+ and a
tyrosine kinase-dependent enhancement of Ca2+ turnover (external Ca2influx and Ca2+ efflux). However, it also attenuates the thrombin-evok
ed cytosolic Ca2+ response by blocking Ca2+ mobilization and slowing t
he rate of external Ca2+ influx. The latter feature would result in a
plasmin-induced inhibition of thrombogenesis.