Duality of plasmin effect on cytosolic free calcium in human platelets.
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.
Nakamura
K
K
Hypertension Research Center, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
Kimura
M
M
Fenton
J W
JW
Andersen
T T
TT
Aviv
A
A
D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood* / Q000493:pharmacokinetics; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology*; D016257:Fura-2; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018179:Receptors, Thrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D010446:Peptide Fragments; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D014443:Tyrosine; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013917:Thrombin; D005341:Fibrinolysin; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2