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Calcium Fluxes in Platelets and Endothelial Cells; Mechanisms and Functional Significance

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Antithrombotics

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 126))

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Abstract

Elevation of cytosolic [Ca2+], [Ca2+]i, is a key excitatory event in both platelet and endothelial cell activation, and hence, may play functionally opposing roles in the pathophysiological mechanisms underlying thrombosis, i.e. elevated platelet [Ca2+]i is pro-aggregatory while elevated endothelial cell [Ca2+]i is anti-aggregatory leading to increased production of prostacyclin and NO. Recent evidence has shown that [Ca2+]i is raised in both cell types by release of Ca2+ from internal stores and by influx via a receptor-mediated Ca2+ entry mechanism distinct from classical voltage-gated Ca2+ channels for which there are many pharmacologial ligands. Furthermore, these Ca2+ influx mechanisms in platelets and endothelial cells are distinguishable, probably reflecting the nature of each cellular response. These developments will be reviewed here in conjunction with other studies which challenge the role of elevated [Ca2+]i as the central, or even necessary, signal for cell activation. Potential consequences of inhibition of Ca2+ flux are considered.

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References

  1. Maclntyre, D.E. and Rink, T.J. (1982) ‘The role of platelet membrane potential in the initiation of platelet aggregation’, Thromb. Haemostas. (Stuttgart) 47, 22.

    Google Scholar 

  2. Doyle, V.M. and Ruegg, U.T. (1985), ‘Lack of evidence for voltage dependent calcium channels on platelets’, Biochem. Biophys. Res. Commun. 127, 161.

    Article  PubMed  CAS  Google Scholar 

  3. Hallam, T.J. and Rink, T.J. (1985), ‘Responses to adenosine diphosphate in human platelets loaded with the fluorescent calcium indicator quin2’, J. Physiol. 368, 131–146.

    PubMed  CAS  Google Scholar 

  4. Jacob, R., Merritt, J.E., Hallam, T.J. and Rink, T.J.(1988), ‘Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells’, Nature 335, 40–45.

    Article  PubMed  CAS  Google Scholar 

  5. Jy, W., Ahn, Y.S., Shanbaky, N., Fernandez, L.F., Harrington, W.J. and Brown, H.E. (1984), ‘Calcium channel blockade for thrombosis and other disorders’, Clin. Res. 32, 494a.

    Google Scholar 

  6. Jy, W., Ahn, Y.S., Shanbaky, N., Fernandez, L.F., Harrington, W.J. and Haynes, D.H. (1987), ‘Abnormal calcium handling by platelets in thrombotic disorders’, Circulation Res. 60, 346–335

    Article  PubMed  CAS  Google Scholar 

  7. Thomas, R.C. (1981), ‘Ion-selective micro-electrodes. In: Techniques in Cellular Physiology’ (Baker P.F. ed.), Vol. P1/11, p125, ppl-12, Elsevier.

    Google Scholar 

  8. Knight, D.E. and Scrutton, M.C. (1980), ‘Direct evidence for a role for Ca2+ in amine storage granule secretion by human platelets’, Thrombosis Res. 20, 437–446.

    Article  CAS  Google Scholar 

  9. Knight, D.E. and Scrutton, M.C. (1980), ‘Gaining access to the cytosol: the technique and applications of electropermeabilization’, Biochem. J. 234, 497–506.

    Google Scholar 

  10. Tsien, R.Y., Pozzan, T. and Rink, T.J. (1982), ‘Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator’, J. Cell. Biol. 94, 335–340.

    Article  PubMed  Google Scholar 

  11. Hamill, O.P., Marty, A., Neher, E., Sakmann, B. and Sigwall, F.J. (1981), “Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches’, Pflugers Arch. 391, 85–100.

    Article  PubMed  CAS  Google Scholar 

  12. Rink T.J. and Pozzan, T. (1985), ‘Using quint in cell suspensions’, Cell Calcium 6, 133.

    Article  PubMed  CAS  Google Scholar 

  13. Hallam, T.J. and Pearson, J.D. (1986), ‘Exogenous ATP raises cytoplasmic free calcium in fura-2 loaded piglet aortic endothelial cells’, FEBS Letts. 207, 95–99.

    Article  CAS  Google Scholar 

  14. Tsien, R.Y., Rink, T.J. and Poenie, M. (1985), ‘Measurement of cytosolic free Ca2+ in individual small cells using fluorescence microscopy with dual excitation wavelengths’, Cell Calcium 6, 145.

    Article  PubMed  CAS  Google Scholar 

  15. Hallam, T.J., Poenie, M. and Tsien, R.Y. (1986), ‘Homogeneity of ADP- and thrombin-stimulated rises in [Ca2+]i in fura-2 loaded human platelet populations revealed by fluorescence ratio image processing’, J. Physiol. 377, 123P.

    Google Scholar 

  16. Hallam, T.J. and Rink, T.J. (1985), ‘Agonists stimulate divalent cation channels in the plasma membrane of human platelets’, FEBS Letts, 186, 175–179.

    Article  CAS  Google Scholar 

  17. Hallam, T.J., Pearson, J.D and Needham, L.A. (1988), ‘Thrombin-stimulated elevation of human endothelial cell cytoplasmic free calcium concentration causes prostacyclin production’, Biochem. J. 251, 243–250.

    PubMed  CAS  Google Scholar 

  18. Streb, H., Irvine, R.F., Berridge, M.J. and Schulz, I. (1983), ‘Release of Ca2+ from a non-mitochondrial intracellular store in pancreatic acinar cells by inositol, 1,4,5-triphosphate’, Nature 306, 67–69.

    Article  PubMed  CAS  Google Scholar 

  19. Magocsi, M., Enyedi, A., Sarkadi, B. and Gardos, G. (1988), ‘Effects of phosphoinositides on calcium movements in human platelet membrane vesicles’, Biochim. Biophys. Acta 944, 202–212.

    Article  PubMed  CAS  Google Scholar 

  20. O’Rourke, F.A., Halenda, S.P., Zavoico, G.B. and Feinstein, M.B. (1985), ‘IP3 release Ca2+ from a Ca2+-transporting membrane vesicle fraction derived from human platelets’, J. Biol. Chem. 260, 956–950.

    PubMed  Google Scholar 

  21. Rittenhouse, S.E. and Sasson, J.P. (1985), ‘Mass changes in IP3 in human platelets stimulated by thrombin’, J. Biol. Chem. 260, 8657–8662.

    PubMed  CAS  Google Scholar 

  22. Fisher, G.J, Bakshian, S. and Baldassare, J.J. (1985), ‘Activation of human platelets by ADP causes a rapid rise in cytosolic free calcium without hydrolysis of phosphatidylinositol 4,5-bisphosphate’, Biochem. Biophys. Res. Commun. 129, 958.

    Article  PubMed  CAS  Google Scholar 

  23. Vickers, J.C., Kinlough-Rathbone, R.L. and Mustard, J.F. (1986), ‘The decrease in phosphatidylinositol 4,5-bisphosphate in ADP-stimulated washed rabbit platelets is not primarily due to phsopholipase C activation’, Biochem. J. 237, 327–332.

    PubMed  CAS  Google Scholar 

  24. Hallam, T.J., Simpson, A.W.M., O’Connor, N. and Rink, T.J. (1985), ‘Control and inter-relation of aggregation and secretion; the roles of Ca2+, diacylglycerol and thromboxane with particular reference to ADP stimulation, In: “Mechanisms of stimulus-response coupling in platelets”, (J. Westwick, M.F. Scully, D.E. Maclntyre and V.V. Kakkar, eds.), Plenum, N.Y., pp145–162.

    Chapter  Google Scholar 

  25. Rink, T.J., Sanchez, A. and Hallam, T.J. (1983), ‘Diacyiglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets’, Nature 305, 317–319.

    Article  PubMed  CAS  Google Scholar 

  26. Rink T.J. and Hallam, T.J. (1984), ‘What turns platelets on?’, Trends Biochem. Sci. 9, 215–219.

    Article  Google Scholar 

  27. Volpe, P., Krause, K., Hashimoto, S., Zorzato, F., Pozzan, T., Meldolesi, J. and Lew, D.P. (1987), ‘Calciosome, a cytoplasmic organelle: The IP3-sensitive Ca2+ store of non-muscle cells?’, Proc. Natl. Acad. Sci (U.S.A.) 85, 1081–1095.

    Google Scholar 

  28. Hallam, T.J., Jacob, R. and Merritt, J.E. (1988), ‘Evidence that agonists stimulate divalent cation influx into human endothelial cells’, Biochem. J. 255, 179–184.

    PubMed  CAS  Google Scholar 

  29. Hallam, T.J., Jacob, R. and Merritt, J.E. (1989), ‘Influx of divalent cations can be independent of receptor stimulation in human endothelial cells’, Biochem. J. 259, 125–129.

    PubMed  CAS  Google Scholar 

  30. Rink, T.J. and Sage, S.O. (1987), ‘Stimulated Ca2+ efflux from fura-2 loaded human platelets’, J. Physiol. 393, 513–524.

    PubMed  CAS  Google Scholar 

  31. Mayer, M.L. and Westbrook, G.L. (1987), ‘Permeation and block of N-methyl D-Aspartic acid receptor channels by divalent cations in mouse cultured central neurones’, J. Physiol. 394, 501–527.

    PubMed  CAS  Google Scholar 

  32. Lansman, J.B., Hallam, T.J and Rink, T.J. (1987), ‘Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers’, Nature 325, 811–813.

    Article  PubMed  CAS  Google Scholar 

  33. Adams, D.J., Lategan, T.W., Lodge, N.J. and van Breemen, C. (1987), ‘Inward rectifying K+-channels and thrombin-activated cation channels in cultured endothelial cells from bovine pulmonary artery’, J. Physiol. 394, 45P.

    Google Scholar 

  34. Johns, A., Lategan, T.W., Lodge, N.J., Ryan, U.S., van Breemen, C. and Adams, D.J. (1987), ‘Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells’, Tissue Cell 19, 733–746.

    Article  PubMed  CAS  Google Scholar 

  35. Bregestovski, P., Bakhramov, S., Danilov, A., Moldobaeva, A. and Takeda, K. (1988), ‘Histamine-induced inward currents in cultured endothelial cells from human umbilical vein’, Br. J. Pharmacol 95, 429–436.

    Article  PubMed  CAS  Google Scholar 

  36. Mahaut-Smith, M.P., Rink, T.J. and Sage, S.O. (1989), ‘Single channels in human platelets activated by ADP’, J. Physiol. 415, 24P.

    Google Scholar 

  37. Zschauer, A., van Breemen, C., Buhler, F.R. and Nelson, M.T. (1988), ‘Calcium channels in thrombin-activated human platelet membranes’, Nature 334, 703–705.

    Article  PubMed  CAS  Google Scholar 

  38. Sage, S.O. and Rink, T.J. (1986), ‘Kinetic differences between thrombin-induced and ADP-induced calcium influx and release from internal stores in fura-2 loaded human platelets’, Biochem, Biophys, Res. Commun. 136, 1124–1129.

    CAS  Google Scholar 

  39. Sage, S.O., Merritt, J.E., Hallam, T.J. and Rink, T.J. (1989), ‘Receptor-mediated calcium entry in fura-2 loaded human platelets stimulated with ADP and thrombin. Dual wavelength studies with Mn2+’, Biochem. J. 258, 923–926.

    PubMed  CAS  Google Scholar 

  40. Penner, R., Mathews, G and Neher, E (1988), ‘Regulation of calcium influx by second messengers in rat mast cells’, Nature 334, 449–504.

    Article  Google Scholar 

  41. Powling, M.J. and Hardisty, R.M. (1985), ‘GPIIb/IIIa complex and Ca2+ influx into stimulated platelets’, Blood 66, 731–734.

    PubMed  CAS  Google Scholar 

  42. Sinigaglia, F., Bisio, A., Torti, M., Balduini, C.L., Bertolino, G. and Balduini, C. (1988), ‘Effect of GPIIb/IIIa complex ligands on calcium movement and cytoskeleton organisation in activated platelets’, Biochem. Biophys. Res. Commun. 154, 258–264.

    Article  PubMed  CAS  Google Scholar 

  43. Pandol, S.J., Schoffield, M.S., Fimmel, C.J. and Muallem, S. (1987), ‘The agonist-sensitive calcium pool in the pancreatic acinar cell. Activation of plasma membrane Ca2+ influx mechanism’, J. Biol. Chem. 262, 16963–16968.

    PubMed  CAS  Google Scholar 

  44. Putney, J.W. (1986), ‘A model for receptor-regulated calcium entry’, Cell Calcium 7, 1–12.

    Article  PubMed  CAS  Google Scholar 

  45. Hallam, T.J. and Rink, T.J. (1989), ‘Receptor-mediated Ca2+ entry: diversity of function and mechanism’, Trends Pharmacol. Sci. 10, 8–10.

    CAS  Google Scholar 

  46. Jacob, R. (1990), ‘Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells’, J. Physiol. 421, 55–77.

    PubMed  CAS  Google Scholar 

  47. Sage, S.O., Reast, R. and Rink, T.J. (1990), ‘ADP evokes biphasic Ca2+ influx in fura-2 loaded human platelets: evidence for Ca2+ entry regulated by the intracellular Ca2+ store’, Biochem. J. 265, 675–680.

    PubMed  CAS  Google Scholar 

  48. Fujimura, K. and Phillips, D.R. (1983), ‘Calcium cation regulation of glycoprotein IIb/IIIa complex formation in platelet plasma membranes’, J. Biol. Chem. 258, 10247–10252.

    PubMed  CAS  Google Scholar 

  49. Packham, M.A., Guccione, M.A., Greenberg, J.P., Kinlough-Rathbone, R.L. and Mustard, J.F. (1977), ‘Release of [14C]-5HT during initial platelet changes induced by thrombin, collagen or A23187’, Blood 50, 915.

    PubMed  CAS  Google Scholar 

  50. Rink, T.J., Smith, S.W. and Tsien, R.Y. (1982), ‘Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca2+-independent activation for shape-change and secretion’, FEES Letts. 148, 21.

    Article  CAS  Google Scholar 

  51. Hallam, T.J., Daniel, J.L., Kendrick-Jones, J. and Rink, T.J. (1985), ‘Relationship between cytoplasmic free calcium and myosin light chain phosophorylation in intact platelets’, Biochem. J. 232, 373–377.

    PubMed  CAS  Google Scholar 

  52. Simpson, A.W.M., Hallam, T.J. and Rink, T.J. (1986), ‘Low concentrations of the stable prostaglandin endoperoxide U44069 stimulate shape change in quin2-loaded platelets without a measurable increase in [Ca2+]I’, FEBS Letts. 201, 301–305.

    Article  CAS  Google Scholar 

  53. Sage, S.O. and Rink, T.J. (1986), ‘Effects of ionic substitution on [Ca2+]i rises evoked by thrombin and PAF in human platelets’, Eur. J. Pharmacol. 128, 99–107.

    Article  PubMed  CAS  Google Scholar 

  54. Carter, T.D., Hallam, T.J., Cusack, N.J. and Pearson, J.D. (1988), ‘Regulation of P2Y-purinoceptor-mediated prostacyclin release from human endothelial cells by cytosolic calcium concentration’, Br. J. Pharmacol. 95, 1181–1190.

    Article  PubMed  CAS  Google Scholar 

  55. Pollock, W.K., Irvine, R.F. and Rink, T.J. (1986), ‘Free Ca2+-requirements of agonist-induced thromboxane A2 synthesis in human platelets’, Eur. J. Pharmac. 132, 309–313.

    Article  CAS  Google Scholar 

  56. Carter, T.D., Hallam, T.J. and Pearson, J.D. (1989), ‘Protein kinase C activation alters the sensitivity of agonist-stimulated endothelial-cell prostacyclin production to intracellular Ca2+’, Biochem, J. 262, 431–437.

    CAS  Google Scholar 

  57. Palmer, R.M.J., Ferrige, A.G. and Moncada, S. (1987), ‘Nitric oxide release accounts for the biological actitivity of EDRF’, Nature 327, 524–526.

    Article  PubMed  CAS  Google Scholar 

  58. Palmer, R.M.J., Ashton, D.S. and Moncada, S. (1988), ‘Vascular endothelial cells synthesise nitric oxide from L-arginine’, Nature 333, 664–666.

    Article  PubMed  CAS  Google Scholar 

  59. Singer, H.A. and Peach, M.J. (1982), ‘Calcium-and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta’, Hypertension 4 (Suppl. II), 19–25.

    PubMed  CAS  Google Scholar 

  60. Gordon, J.L. and Martin, W. (1983), ‘Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells’, Br. J. Pharmacol. 79, 531–541.

    Article  PubMed  CAS  Google Scholar 

  61. Griffith, T.M., Edwards, D.H., Lewis, M.J., Newby, A.C., Lewis, M.J. and Henderson, A.H. (1986), ‘Production of EDRF is dependent on oxidative phosphorylation and extracellular calcium’, Cardiovasc, Res. 20, 7–12.

    Article  CAS  Google Scholar 

  62. Lewis, M.J. and Henderson, A.H. (1987), ‘A phorbol ester inhibits the release of EDRF’, Eur. J. Pharmacol. 137, 167–171.

    Article  PubMed  CAS  Google Scholar 

  63. Sage, S.O., Adams, D.J. and van Breemen, C. (1989), ‘Synchronised oscillations in cytoplasmic free calcium concentration in confluent bradykinin-stimulated bovine pulmonary artery endothelial cell monolayers’, J. Biol. Chem. 264, 6–9.

    PubMed  CAS  Google Scholar 

  64. Campbell, K.P, Leung, A.T. and Sharp, A.H. (1988), ‘The biochemistry and molecular biology of the dihydropyridine-sensitive Ca2+ channel’, Trends Neurosci. 11, 425–430.

    Article  PubMed  CAS  Google Scholar 

  65. Tsien, R.W., Lipscombe, D., Madison, D.V., Bley, R.R. and Fox, A.P. (1988), ‘Multiple types of neuronal calcium channels and their selective modulation’, Trends Neurosci. 11, 431–438.

    Article  PubMed  CAS  Google Scholar 

  66. Avdonin, P.V., Merishikov, M.Y., Svitina-Ulitina, I.V. and Tkachuk, V.A. (1988), ‘Blocking of the receptor-stimulated calcium entry into human platelets by verapamil and nicardipine’, Thrombos Res. 52, 587–597.

    Article  CAS  Google Scholar 

  67. Spedding, M., Schini, V., Schoeffter, P. and Miller, R.C. (1986), ‘Calcium channel activation does not increase release of EDRF in rat aorta although tonic release of EDRF may modulate calcium channel activity in smooth muscle’, J. Cardiovasc. Pharmacol. 8, 1130–1137.

    Article  PubMed  CAS  Google Scholar 

  68. Merritt, J.E., Armstrong, W.P., Benham, C.D., Hallam, T.J., Jacob, R., Jaxa-Chamiec, A.A., Leigh, B.K., McCarthy, S.A., Moores, K.E. and Rink, T.J. (1990) ‘SK+F 96365, a novel inhibitor of receptor-mediated calcium entry’, Biochem. J. 271, 515–522.

    PubMed  CAS  Google Scholar 

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  1. Trevor J. Hallam
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Editors and Affiliations

  1. University of Antwerp (UIA)., Antwerp, Belgium

    Arnold G. Herman (Professor of Pharmacology) (Professor of Pharmacology)

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Hallam, T.J. (1991). Calcium Fluxes in Platelets and Endothelial Cells; Mechanisms and Functional Significance. In: Herman, A.G. (eds) Antithrombotics. Developments in Cardiovascular Medicine, vol 126. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3484-2_6

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  • DOI: https://doi.org/10.1007/978-94-011-3484-2_6

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