Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Jul;80(1):267–271. doi: 10.1172/JCI113058

Synergism of platelet-aggregating agents. Role of elevation of cytoplasmic calcium.

J A Ware, M Smith, E W Salzman
PMCID: PMC442228  PMID: 3110213

Abstract

When a pair of platelet agonists, each in subthreshold concentration, is added together or in sequence to a platelet suspension, the platelet response is enhanced. Addition of two agonists to platelets loaded with aequorin also enhanced the observed rise in cytoplasmic ionized calcium ([Ca2+]i) in response to the second agonist if the agonists were added within 20 s of each other. Enhancement of aggregation and secretion required that an increase in [Ca2+]i (as indicated by aequorin but not necessarily indo-1) followed the first agonist, but not that the [Ca2+]i remain elevated until addition of the second agonist. Enhancement was not prevented by aspirin, ADP scavengers, or chelators of extracellular Ca2+. We conclude that a rise in [Ca2+]i induced by a first agonist "primes" platelets for an augmented functional response to a second agonist, which is not, however, determined by the [Ca2+]i at the time of addition of the second agonist.

Full text

PDF
269

Images in this article

Selected References

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

  1. Ardlie N. G., Cameron H. A., Garrett J. Platelet activation by circulating levels of hormones: a possible link in coronary heart disease. Thromb Res. 1984 Nov 15;36(4):315–322. doi: 10.1016/0049-3848(84)90322-0. [DOI] [PubMed] [Google Scholar]
  2. Best L. C., Holland T. K., Jones P. B., Russell R. G. The interrelationship between thromboxane biosynthesis, aggregation and 5-hydroxytryptamine secretion in human platelets in vitro. Thromb Haemost. 1980 Feb 29;43(1):38–40. [PubMed] [Google Scholar]
  3. Buttrick P. M., Forscher C. A., Sussman I. I., Mueller H. S. Sub-aggregatory doses of catecholamines prevent prostacyclin-induced inhibition of platelet aggregation. Am Heart J. 1985 Jun;109(6):1258–1263. doi: 10.1016/0002-8703(85)90348-5. [DOI] [PubMed] [Google Scholar]
  4. Figures W. R., Scearce L. M., Wachtfogel Y., Chen J., Colman R. F., Colman R. W. Platelet ADP receptor and alpha 2-adrenoreceptor interaction. Evidence for an ADP requirement for epinephrine-induced platelet activation and an influence of epinephrine on ADP binding. J Biol Chem. 1986 May 5;261(13):5981–5986. [PubMed] [Google Scholar]
  5. Grant J. A., Scrutton M. C. Positive interaction between agonists in the aggregation response of human blood platelets: interation between ADP, adrenaline and vasopressin. Br J Haematol. 1980 Jan;44(1):109–125. doi: 10.1111/j.1365-2141.1980.tb01189.x. [DOI] [PubMed] [Google Scholar]
  6. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  7. Hallam T. J., Scrutton M. C., Wallis R. B. Synergistic responses and receptor occupancy in rabbit blood platelets. Thromb Res. 1982 Aug 15;27(4):435–445. doi: 10.1016/0049-3848(82)90061-5. [DOI] [PubMed] [Google Scholar]
  8. Johnson P. C., Ware J. A., Cliveden P. B., Smith M., Dvorak A. M., Salzman E. W. Measurement of ionized calcium in blood platelets with the photoprotein aequorin. Comparison with Quin 2. J Biol Chem. 1985 Feb 25;260(4):2069–2076. [PubMed] [Google Scholar]
  9. Johnson P. C., Ware J. A., Salzman E. W. Concurrent measurement of platelet ionized calcium concentration and aggregation: studies with the lumiaggregometer. Thromb Res. 1985 Nov 15;40(4):435–443. doi: 10.1016/0049-3848(85)90280-4. [DOI] [PubMed] [Google Scholar]
  10. Packham M. A., Guccione M. A., Chang P. L., Mustard J. F. Platelet aggregation and release: effects of low concentrations of thrombin or collagen. Am J Physiol. 1973 Jul;225(1):38–47. doi: 10.1152/ajplegacy.1973.225.1.38. [DOI] [PubMed] [Google Scholar]
  11. Rao G. H., Johnson G. J., White J. G. Influence of epinephrine on the aggregation response of aspirin-treated platelets. Prostaglandins Med. 1980 Jul;5(1):45–58. doi: 10.1016/0161-4630(80)90090-7. [DOI] [PubMed] [Google Scholar]
  12. Steen V. M., Holmsen H. Synergism between thrombin and epinephrine in human platelets: different dose-response relationships for aggregation and dense granule secretion. Thromb Haemost. 1985 Oct 30;54(3):680–683. [PubMed] [Google Scholar]
  13. Ware J. A., Johnson P. C., Smith M., Salzman E. W. Effect of common agonists on cytoplasmic ionized calcium concentration in platelets. Measurement with 2-methyl-6-methoxy 8-nitroquinoline (quin2) and aequorin. J Clin Invest. 1986 Mar;77(3):878–886. doi: 10.1172/JCI112385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ware J. A., Johnson P. C., Smith M., Salzman E. W. Inhibition of human platelet aggregation and cytoplasmic calcium response by calcium antagonists: studies with aequorin and quin2. Circ Res. 1986 Jul;59(1):39–42. doi: 10.1161/01.res.59.1.39. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES