Agonist Stimulated Changes in Human Endothelial Cell Cytosolic Calcium

  • Trevor J. Hallam
  • J. E. Merritt
  • T. J. Rink
  • R. Jacob


A considerable amount of evidence exists to suggest that a rise in cytoplasmic free calcium concentration, [Ca2+]i, evokes morphological, metabolic and secretory responses in endothelial cells in response to stimulation by many inflammatory mediators. One of the most potent agents for stimulating the release of the vasodilators endothelial-derived relaxing factor (EDRF) and prostacyclin (PGI2) is the calcium ionophore A23187. However, the hypothesis that elevated [Ca2+]i is the physiological messenger is held with some caution since A23187-evoked rises in [Ca2+]i sufficient to evoke these responses can conceivably be far larger than those physiologically attained on stimulation with inflammatory mediators. With the development of the fluorescent [Ca2+] indicator dyes quin2, fura-2 and indo-1, increases in [Ca2+]. have been observed in endothelial cells from bovine or porcine aortae or from human umbilical vein in response to histamine, bradykinin, thrombin, adenine nucleotides and PAF. Furthermore, recent work has shown that these mediator-evoked rises in [Ca2+]i are both sufficient and necessary for the production and release of PGI2 (Hallam et al., 1988c). Our attention has now focussed on the mechanisms of Ca2+ movement and the sources of trigger Ca2+.


Endothelial Cell Human Umbilical Vein Endothelial Cell Human Endothelial Cell Intracellular Store Calcium Ionophore A23187 
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  1. Adams, D.J., Lategan, T.W., Lodge, N.J. and van Breemen, C. Inward rectifying K+ channels and thrombin-activated cation channels in cultured endothelial cells from bovine pulmonary artery. J. Physiol. 394:45, 1987.Google Scholar
  2. Benham, C.D. and Tsien, R.W. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature. 328:275–278, 1987.PubMedCrossRefGoogle Scholar
  3. Bussolino, F., Aglieita, M., Sanavaio, F., Stacchini, A., Lauri, D. and Camussi, G. Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells. J. Immunol. 135:2748–2753, 1985.PubMedGoogle Scholar
  4. Crutchley, D.J., Ryan, J.W., Ryan, U.S. and Fisher, G.H. Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists. Biochim. Biophys. Acta. 751:99–107, 1983.PubMedCrossRefGoogle Scholar
  5. D’Amore, P. and Shepro, D. Stimulation of growth and calcium influx in cultured bovine, aortic endothelial cells by platelets and vasoactive substances. J. Cell Physiol. 92: 177–184, 1977.PubMedCrossRefGoogle Scholar
  6. Guth, P.H. and Hirabayashi, K. The effect of histamine on microvascular permeability in the muscularis externa of rat small intestine. Microvasc. Res. 25:322–332, 1983.PubMedCrossRefGoogle Scholar
  7. Hallam, T.J. and Pearson, J.D. Exogenous ATP raises cytoplasmic free calcium in fura-2 loaded piglet aortic endothelial cells. FEBS Letts. 207:95–99, 1986.CrossRefGoogle Scholar
  8. Hallam, T.J. and Rink, T.J. Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Letts. 186:175–179, 1985.CrossRefGoogle Scholar
  9. Hallam, T.J., Jacob, R. and Merritt, J.E. Evidence that agonists stimulate divalent cation influx into human endothelial cells. Biochem. J. 255:179–184, 1988a.PubMedGoogle Scholar
  10. Hallam, T.J., Jacob, R. and Merritt, J.E. Influx of divalent cations into the cytoplasm of human endothelial cells can be independent of receptor stimulation. Biochem. J. 259:125–129, 1989.PubMedGoogle Scholar
  11. Hamilton, K.K. and Sims, P.J. Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1. J. Clin. Invest. 79:600–608, 1987.PubMedCrossRefGoogle Scholar
  12. Irvine R.F. and Moore, R.M. Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem. J. 240:917–920, 1986.PubMedGoogle Scholar
  13. Jacob, R., Merritt, J.E., Hallam, T.J. and Rink, T.J. Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells. Nature. 335:40–45, 1988.PubMedCrossRefGoogle Scholar
  14. Johns, A., Lategan, T.W., Lodge, N.J.., Ryan, U.S., van Breemen, C. and Adams, D.J. Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells. Tissue and Cell. 733–745, 1987.Google Scholar
  15. Killackey, J.J.F., Johnston, M.G. and Movat, H.Z. Increased permeability of microcarrier-cultured endothelial monolayers in response to histamine and thrombin. A model for the in vitro study of increased vasopermeability. Am. J. Pathol. 122:50–61, 1986.PubMedGoogle Scholar
  16. Lambert, T.L., Kent, R.S. and Whorton, A.R. Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells. J. Biol. Chem. 261:15288–15293, 1986.PubMedGoogle Scholar
  17. Lansman, J.B., Hallam, T.J. and Rink, T.J. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? Nature. 325:811–813, 1987.PubMedCrossRefGoogle Scholar
  18. McIntyre, T.M„ Zimmerman, G.A., Satoh, K. and Prescott, S.M. Cultured endothelial cells synthesise both PAF and prostacyclin in response to histamine, bradykinin and ATP. J. Clin. Invest. 76:271–280, 1985.PubMedCrossRefGoogle Scholar
  19. Resink, T.J., Gregorian, G.Y., Moldabaeva, A.K., Danilov, S.M. and Buhler, F. Histamine-induced phosphoinositide metabolism in cultured human umbilical vein endothelial cells. Association with thromboxane and prostacyclin release. Biochem. Biophys. Res. Comm. 144:438–446, 1987.PubMedCrossRefGoogle Scholar
  20. Rotrosen, D. and Gallin, J.I. Histamine Type I receptor occupancy increases endothelial cell cytosolic calcium, reduces F-actin, and promotes albumin diffusion across cultured endothelial monolayers. J. Cell Biol. 103:2379–2387, 1986.PubMedCrossRefGoogle Scholar
  21. Rubanyi, G.M., Schwartz, A.M. and Vanhoutte, P.M. The calcium channel agonists Bay K8644 and (+)202,791 stimulate the release of EDRF from canine femoral arteries. Eur. J. Pharmacol. 117:143–144, 1985.PubMedCrossRefGoogle Scholar
  22. Spedding, M., Schini, V., Schoeffter, P. and Miller, R.C. 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. Pharmol. 8:1130–1137, 1986.CrossRefGoogle Scholar
  23. von Tscharner, V., Prod’hom, B., Baggiolini, M. and Reuter, H. Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. Nature 324:369–372, 1986.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Trevor J. Hallam
    • 1
  • J. E. Merritt
    • 1
  • T. J. Rink
    • 1
  • R. Jacob
    • 1
  1. 1.Department of Cellular PharmacologySmith Kline and French Research Ltd.Welwyn, HertfordshireUK

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