Duality of plasmin effect on cytosolic free calcium in human platelets
Nakamura, K.; Kimura, M.; Fenton, J.W.; Andersen, T.T.; Aviv, A.
American Journal of Physiology 268(4 Pt 1): C958-C967
1995
ISSN/ISBN: 0002-9513 PMID: 7733244 Document Number: 442470
Plasmin caused a modest and gradual increase in platelet cytosolic Ca-2+, mediated through both Ca-2+ mobilization and external Ca-2+ entry. This response was associated with accelerated Ca-2+ extrusion and protein tyrosine phosphorylation. Plasmin-enhanced external Ca-2+ entry and Ca-2+ extrusion (but not Ca-2+ mobilization) were attenuated by the tyrosine kinase inhibitor, genistein. Plasmin inhibited the thrombin-evoked increase in cytosolic Ca-2+ and also inhibited the Ca-2+ 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 Ca-2+ and a tyrosine kinase-dependent enhancement of Ca-2+ turnover (external Ca-2+ influx and Ca-2+ efflux). However, it also attenuates the thrombin-evoked cytosolic Ca-2+ response by blocking Ca-2+ mobilization and slowing the rate of external Ca-2+ influx. The latter feature would result in a plasmin-induced inhibition of thrombogenesis.