AJP - Cell Physiology, Vol 268, Issue 4 C958-C967, Copyright © 1995 by American Physiological Society
Duality of plasmin effect on cytosolic free calcium in human platelets
K. Nakamura, M. Kimura, J. W. Fenton 2nd, T. T. Andersen and A. Aviv
Hypertension Research Center, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
Plasmin caused a modest and gradual increase in platelet cytosolic Ca2+,
mediated through both Ca2+ mobilization and external Ca2+ entry. This
response was associated with accelerated Ca2+ extrusion and protein
tyrosine phosphorylation. Plasmin-enhanced external Ca2+ entry and Ca2+
extrusion (but not Ca2+ mobilization) were attenuated by the tyrosine
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, plasmin inhibited the
binding of 125I-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 was not reversed by protein
kinase C inhibitors. Plasmin did not change platelet cyclic nucleotides.
These results suggest a dual effect of plasmin. Plasmin produces a small
rise in platelet cytosolic Ca2+ and a tyrosine kinase-dependent enhancement
of Ca2+ turnover (external Ca2+ influx and Ca2+ efflux). However, it also
attenuates the thrombin-evoked cytosolic Ca2+ response by blocking Ca2+
mobilization and slowing the rate of external Ca2+ influx. The latter
feature would result in a plasmin-induced inhibition of thrombogenesis.
