Duality of plasmin effect on cytosolic free calcium in human platelets

K. Nakamura, M. Kimura, J. W. Fenton, T. T. Andersen, Abraham Aviv

Research output: Contribution to journal › Article

18 Citations (Scopus)

Abstract

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 α-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume268
Issue number4 37-4
StatePublished - Jan 1 1995

Fingerprint

Fibrinolysin
Blood Platelets
Calcium
Thrombin
Protein-Tyrosine Kinases
Protein Kinase C
Thrombin Receptors
Protein C Inhibitor
Genistein
Cyclic Nucleotides
Protein Kinase Inhibitors
Tyrosine
Phosphorylation
Peptides

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Keywords

  • cyclic nucleotides
  • protein kinase C
  • protein tyrosine kinase
  • receptors
  • thrombin

Cite this

Nakamura, K. ; Kimura, M. ; Fenton, J. W. ; Andersen, T. T. ; Aviv, Abraham. / Duality of plasmin effect on cytosolic free calcium in human platelets. In: American Journal of Physiology - Cell Physiology. 1995 ; Vol. 268, No. 4 37-4.
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Nakamura, K, Kimura, M, Fenton, JW, Andersen, TT & Aviv, A 1995, 'Duality of plasmin effect on cytosolic free calcium in human platelets', American Journal of Physiology - Cell Physiology, vol. 268, no. 4 37-4.

Duality of plasmin effect on cytosolic free calcium in human platelets. / Nakamura, K.; Kimura, M.; Fenton, J. W.; Andersen, T. T.; Aviv, Abraham.

In: American Journal of Physiology - Cell Physiology, Vol. 268, No. 4 37-4, 01.01.1995.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Duality of plasmin effect on cytosolic free calcium in human platelets

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N2 - 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 α-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.

AB - 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 α-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.

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Nakamura K, Kimura M, Fenton JW, Andersen TT, Aviv A. Duality of plasmin effect on cytosolic free calcium in human platelets. American Journal of Physiology - Cell Physiology. 1995 Jan 1;268(4 37-4).

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