Cargando…
THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS
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 ha...
Autores principales: | , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1974
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2109156/ https://www.ncbi.nlm.nih.gov/pubmed/4360292 |
_version_ | 1782139214562852864 |
---|---|
author | Zucker, Marjorie B. Troll, Walter Belman, Sidney |
author_facet | Zucker, Marjorie B. Troll, Walter Belman, Sidney |
author_sort | Zucker, Marjorie B. |
collection | PubMed |
description | 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 E(1). 1 µM did not release β-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. |
format | Text |
id | pubmed-2109156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1974 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21091562008-05-01 THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS Zucker, Marjorie B. Troll, Walter Belman, Sidney J Cell Biol Article 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 E(1). 1 µM did not release β-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. The Rockefeller University Press 1974-02-01 /pmc/articles/PMC2109156/ /pubmed/4360292 Text en Copyright © 1974 by The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Zucker, Marjorie B. Troll, Walter Belman, Sidney THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title | THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title_full | THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title_fullStr | THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title_full_unstemmed | THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title_short | THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS |
title_sort | tumor-promoter phorbol ester (12-0-tetradecanoyl-phorbol-13-acetate), a potent aggregating agent for blood platelets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2109156/ https://www.ncbi.nlm.nih.gov/pubmed/4360292 |
work_keys_str_mv | AT zuckermarjorieb thetumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets AT trollwalter thetumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets AT belmansidney thetumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets AT zuckermarjorieb tumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets AT trollwalter tumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets AT belmansidney tumorpromoterphorbolester120tetradecanoylphorbol13acetateapotentaggregatingagentforbloodplatelets |