Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1987 Nov 1;247(3):669–674. doi: 10.1042/bj2470669

Modulation of platelet-activating-factor-induced calcium influx and intracellular calcium release in platelets by phorbol esters.

F H Valone 1, B Johnson 1
PMCID: PMC1148464  PMID: 3322269

Abstract

The mechanisms by which platelet-activating factor (PAF) and thrombin increase intracellular calcium were examined. Platelets were loaded with the calcium-sensitive fluorescent probe Quin 2 and then were suspended in buffer containing 0.5 mM-Mn2+ in order to quantify simultaneously calcium release from intracellular stores and divalent cation influx. Pretreating platelets with agents which activate protein kinase C [the phorbol ester phorbol myristate acetate (PMA) or the diacylglycerol 1-oleoyl-2-acetylglycerol (OAG)] inhibited increased intracellular calcium by PAF and thrombin in a dose-related manner. That protein kinase C regulates intracellular calcium by phosphorylating proteins in two distinct pathways was suggested by two observations. PAF-induced calcium release was more sensitive to inhibition by PMA and OAG than was manganese influx and the kinetics of recovery from inhibition were different for the two pathways. Both PMA and OAG aggregated Quin 2-loaded platelets without eliciting measurable increases in intracellular calcium. In contrast, prostacyclin, which increases intracellular cyclic AMP, inhibited calcium release and influx in parallel, suggesting that this agent acts at a step common to both pathways.

Full text

PDF
669

Selected References

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

  1. Authi K. S., Evenden B. J., Crawford N. Metabolic and functional consequences of introducing inositol 1,4,5-trisphosphate into saponin-permeabilized human platelets. Biochem J. 1986 Feb 1;233(3):707–718. doi: 10.1042/bj2330707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  3. Billah M. M., Lapetina E. G., Cuatrecasas P. Phosphatidylinositol-specific phospholipase-C of platelets: association with 1,2-diacyglycerol-kinase and inhibition by cyclic-AMP. Biochem Biophys Res Commun. 1979 Sep 12;90(1):92–98. doi: 10.1016/0006-291x(79)91594-8. [DOI] [PubMed] [Google Scholar]
  4. Clare K. A., Scrutton M. C. The role of Ca2+ uptake in the response of human platelets to adrenaline and to 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor). Eur J Biochem. 1984 Apr 2;140(1):129–136. doi: 10.1111/j.1432-1033.1984.tb08075.x. [DOI] [PubMed] [Google Scholar]
  5. Doyle V. M., Rüegg U. T. Lack of evidence for voltage dependent calcium channels on platelets. Biochem Biophys Res Commun. 1985 Feb 28;127(1):161–167. doi: 10.1016/s0006-291x(85)80139-x. [DOI] [PubMed] [Google Scholar]
  6. Hallam T. J., Rink T. J. Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Lett. 1985 Jul 8;186(2):175–179. doi: 10.1016/0014-5793(85)80703-1. [DOI] [PubMed] [Google Scholar]
  7. Hallam T. J., Sanchez A., Rink T. J. Stimulus-response coupling in human platelets. Changes evoked by platelet-activating factor in cytoplasmic free calcium monitored with the fluorescent calcium indicator quin2. Biochem J. 1984 Mar 15;218(3):819–827. doi: 10.1042/bj2180819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Homma H., Kumar R., Hanahan D. J. Some unique features of the metabolic conversion of platelet-activating factor (AGEPC) to alkyl acyl PC by washed rabbit platelets. Arch Biochem Biophys. 1987 Jan;252(1):259–268. doi: 10.1016/0003-9861(87)90030-0. [DOI] [PubMed] [Google Scholar]
  9. Jakobs K. H., Bauer S., Watanabe Y. Modulation of adenylate cyclase of human platelets by phorbol ester. Impairment of the hormone-sensitive inhibitory pathway. Eur J Biochem. 1985 Sep 2;151(2):425–430. doi: 10.1111/j.1432-1033.1985.tb09119.x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Knight D. E., Scrutton M. C. Cyclic nucleotides control a system which regulates Ca2+ sensitivity of platelet secretion. Nature. 1984 May 3;309(5963):66–68. doi: 10.1038/309066a0. [DOI] [PubMed] [Google Scholar]
  12. Orellana S. A., Solski P. A., Brown J. H. Phorbol ester inhibits phosphoinositide hydrolysis and calcium mobilization in cultured astrocytoma cells. J Biol Chem. 1985 May 10;260(9):5236–5239. [PubMed] [Google Scholar]
  13. Rao G. H., Peller J. D., Semba C. P., White J. G. Influence of the calcium-sensitive fluorophore, Quin 2, on platelet function. Blood. 1986 Feb;67(2):354–361. [PubMed] [Google Scholar]
  14. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Simon M. F., Chap H., Douste-Blazy L. Selective inhibition of human platelet phospholipase A2 by buffering cytoplasmic calcium with the fluorescent indicator quin 2. Evidence for different calcium sensitivities of phospholipases A2 and C. Biochim Biophys Acta. 1986 Feb 12;875(2):157–164. doi: 10.1016/0005-2760(86)90164-5. [DOI] [PubMed] [Google Scholar]
  16. Valone F. H., Coles E., Reinhold V. R., Goetzl E. J. Specific binding of phospholipid platelet-activating factor by human platelets. J Immunol. 1982 Oct;129(4):1637–1641. [PubMed] [Google Scholar]
  17. Valone F. H. Inhibition of platelet-activating factor binding to human platelets by calcium channel blockers. Thromb Res. 1987 Mar 1;45(5):427–435. doi: 10.1016/0049-3848(87)90306-9. [DOI] [PubMed] [Google Scholar]
  18. Valone F. H., Johnson B. Decay of the activating signal after platelet stimulation with 1-0-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine: changes in calcium permeability. Thromb Res. 1985 Nov 1;40(3):385–392. doi: 10.1016/0049-3848(85)90273-7. [DOI] [PubMed] [Google Scholar]
  19. Valone F. H., Johnson B. Modulation of cytoplasmic calcium in human platelets by the phospholipid platelet-activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine. J Immunol. 1985 Feb;134(2):1120–1124. [PubMed] [Google Scholar]
  20. Wade P. J., Lunt D. O., Lad N., Tuffin D. P., McCullagh K. G. Effect of calcium and calcium antagonists on [3H]-Paf-acether binding to washed human platelets. Thromb Res. 1986 Jan 15;41(2):251–262. doi: 10.1016/0049-3848(86)90233-1. [DOI] [PubMed] [Google Scholar]
  21. Ware J. A., Johnson P. C., Smith M., Salzman E. W. Aequorin detects increased cytoplasmic calcium in platelets stimulated with phorbol ester or diacylglycerol. Biochem Biophys Res Commun. 1985 Nov 27;133(1):98–104. doi: 10.1016/0006-291x(85)91846-7. [DOI] [PubMed] [Google Scholar]
  22. de Chaffoy de Courcelles D., Roevens P., van Belle H. 12-O-Tetradecanoylphorbol 13-acetate stimulates inositol lipid phosphorylation in intact human platelets. FEBS Lett. 1984 Aug 6;173(2):389–393. doi: 10.1016/0014-5793(84)80811-x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES