The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor-promoting agent, caused irreversible platelet aggregation when more than 0.02 µM was stirred with human citrated or heparinized platelet-rich plasma (PRP). With washed platelets, 1 nM was effective. The alcohol phorbol, which has little tumor-promoting activity, failed to cause platelet aggregation. With all but low concentrations of phorbol ester, aggregation was succeeded by a rapid phase. The latter was prevented or reduced by enzymes which destroy ADP and by aspirin, was associated with a change in platelet shape, and was presumably due to released ADP. At higher concentrations, only a rapid phase was seen, and these inhibitors were not effective. Low concentrations did not aggregate platelets in PRP containing sufficient EDTA or EGTA to chelate ionized calcium or in PRP from thrombasthenic patients; higher concentrations caused slight aggregation. Both the primary, non-ADP-dependent aggregation and the rapid ADP-dependent aggregation were markedly inhibited by substances which increase cyclic AMP, metabolic inhibitors, and the sulfhydryl inhibitor N-ethylmaleimide. Phorbol ester reduced platelet cyclic AMP only when it had been previously elevated by prostaglandin E1. 1 µM did not release ß-glucuronidase, lactic dehydrogenase, or inflammatory material from platelets in 4–5 min despite marked aggregation, but liberated all three in 30 min. The possibility is discussed that low phorbol ester concentrations cause primary aggregation by a direct action on platelet actomyosin.
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1 February 1974
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February 01 1974
THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS
Marjorie B. Zucker,
Marjorie B. Zucker
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
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Walter Troll,
Walter Troll
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
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Sidney Belman
Sidney Belman
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
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Marjorie B. Zucker
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
Walter Troll
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
Sidney Belman
From the Departments of Pathology and Environmental Medicine, New York University School of Medicine, New York 10016
Received:
February 14 1973
Revision Received:
October 16 1973
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Copyright © 1974 by The Rockefeller University Press
1974
J Cell Biol (1974) 60 (2): 325–336.
Article history
Received:
February 14 1973
Revision Received:
October 16 1973
Citation
Marjorie B. Zucker, Walter Troll, Sidney Belman; THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS . J Cell Biol 1 February 1974; 60 (2): 325–336. doi: https://doi.org/10.1083/jcb.60.2.325
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