Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1974 May;75(2):301–314.

Investigation of the Release Reaction in Platelets Exposed to Phorbol Myristate Acetate

James G White, Gundu H R Rao, Richard D Estensen
PMCID: PMC1910840  PMID: 4362915

Abstract

Phorbol myristate acetate (PMA), the active principle of croton oil, is a potent platelet aggregating agent. Previous cytochemical and electron microscopic studies demonstrated that PMA caused selective labilization of platelet storage granules resulting in their conversion to distended vacuoles. Communication was established between the enlarged, almost empty vacuoles and the surrounding plasma through channels of the open canalicular system. The present study has explored the possibility that the effect of PMA on platelet storage organelles stimulates a process of secretion. Analysis of the release reaction in platelets after exposure to PMA revealed that significant amounts of serotonin and adenine nucleotides were secreted without loss of lactic dehydrogenase. Release took place well before the onset of irreversible aggregation. Inhibitors of platelet secretion or ADP induced aggregation could modify or prevent the irreversible clumping stimulated by small concentrations of PMA. Although the secretion induced by PMA differed from the release caused by other agents, the findings of the present study indicate that PMA is capable of triggering the platelet release reaction.

Full text

PDF
301

Images in this article

313Fig 1
on p.313
313Fig 2
on p.313
314Figs 3 and 4
on p.314

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CROSTI P. F., LUCCHELLI P. E. An easy method to determine the serotonin content of human platelets. J Clin Pathol. 1962 Mar;15:191–193. doi: 10.1136/jcp.15.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clawson C. C., White J. G. Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors. Am J Pathol. 1971 Nov;65(2):367–380. [PMC free article] [PubMed] [Google Scholar]
  3. Estensen R. D., White J. G. Ultrastructural features on the platelet response to phorbol myristate acetate. Am J Pathol. 1974 Mar;74(3):441–452. [PMC free article] [PubMed] [Google Scholar]
  4. Hecker E. Cocarcinogenic principles from the seed oil of Croton tiglium and from other Euphorbiaceae. Cancer Res. 1968 Nov;28(11):2338–2349. [PubMed] [Google Scholar]
  5. Holmsen H., Storm E., Day H. J. Determination of ATP and ADP in blood platelets: a modification of the firefly luciferase assay for plasma. Anal Biochem. 1972 Apr;46(2):489–501. doi: 10.1016/0003-2697(72)90323-5. [DOI] [PubMed] [Google Scholar]
  6. Jerushalmy Z., Zucker M. B. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thromb Diath Haemorrh. 1966 May 15;15(3):413–419. [PubMed] [Google Scholar]
  7. Leathwood P. D., Gilford M. K., Plummer D. T. Enzymes in rat urine: lactate dehydrogenase. Enzymologia. 1972 Apr 28;42(4):285–301. [PubMed] [Google Scholar]
  8. Mustard J. F., Packham M. A. Factors influencing platelet function: adhesion, release, and aggregation. Pharmacol Rev. 1970 Jun;22(2):97–187. [PubMed] [Google Scholar]
  9. Van Duuren B. L. Tumor-promoting agents in two-stage carcinogenesis. Prog Exp Tumor Res. 1969;11:31–68. doi: 10.1159/000391388. [DOI] [PubMed] [Google Scholar]
  10. Walsh P. N. Albumin density gradient separation and washing of platelets and the study of platelet coagulant activities. Br J Haematol. 1972 Feb;22(2):205–217. doi: 10.1111/j.1365-2141.1972.tb08801.x. [DOI] [PubMed] [Google Scholar]
  11. White J. G. Effects of cationic polypeptides on thrombasthenic and afibrinogenemic blood platelets. Am J Pathol. 1972 Sep;68(3):447–460. [PMC free article] [PubMed] [Google Scholar]
  12. White J. G., Estensen R. D. Cytochemical electron microscopic studies of the action of phorbol myristate acetate on platelets. Am J Pathol. 1974 Mar;74(3):453–466. [PMC free article] [PubMed] [Google Scholar]
  13. White J. G., Estensen R. D. Degranulation of discoid platelets. Am J Pathol. 1972 Aug;68(2):289–302. [PMC free article] [PubMed] [Google Scholar]
  14. White J. G., Estensen R. D. Selective labilization of specific granules in polymorphonuclear leukocytes by phorbol myristate acetate. Am J Pathol. 1974 Apr;75(1):45–60. [PMC free article] [PubMed] [Google Scholar]
  15. White J. G. Fine structural alterations induced in platelets by adenosine diphosphate. Blood. 1968 May;31(5):604–622. [PubMed] [Google Scholar]
  16. White J. G. The interplatelet zone. Am J Pathol. 1970 Jan;58(1):19–29. [PMC free article] [PubMed] [Google Scholar]
  17. White J. G. Uptake of latex particles by blood platelets: phagocytosis or sequestration? Am J Pathol. 1972 Dec;69(3):439–458. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES