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The effects of TMB-8 on the shape changes of vascular endothelial cells resulting from exposure to various inflammatory agents

  • Inflammation and Immunomodulation
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Abstract

Pre-treatment of the endothelial cells lining the guinea pig inferior vena cava with 8-(diethylamino) octyl 3,4,5-trimethoxybenzoate (TMB-8) (10 μM)in vitro significantly reduced the shape changes resulting from subsequent exposure to platelet activating factor (PAF) (0.1 μM), calcium ionophore A23187 (10 μM), histamine (300 μM), bradykinin (2 μM), prostaglandin E2 (PGE2) (30 μM), or leukotrienes (LT) C4, D4 or E4 (1 μM). Since TMB-8 is an intracellular calcium antagonist, this provides evidence to support the suggestion that these inflammatory agents increase the concentration of intracellular calcium which brings about a contraction of the actin-myosin complex resulting in endothelial cell shape changes, and the formation of interendothelial cell gaps.

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References

  1. G. Majno, V. Gilmore and M. Leventhal,On the mechanism of vascular leakage caused by histamine-type mediators. Circulation Res.21, 833–847 (1967).

    PubMed  Google Scholar 

  2. G. Majno, S. M. Shea and M. Leventhal,Endothelial contraction induced by histamine-type mediators. An electron microscopic study. J. Cell. Biol.42, 647–672 (1969).

    Article  PubMed  Google Scholar 

  3. I. Joris, G. Majno and G. B. Ryan,Endothelial contraction in vivo: a study of the rat mesentery. Virchows Arch. Abt. B Zellpath.12, 73–83 (1972).

    Google Scholar 

  4. D. M. Shasby, S. E. Lind, S. S. Shasby, J. C. Goldsmith and G. W. Hunninghake,Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis. Blood65, 605–614 (1985).

    PubMed  Google Scholar 

  5. F. Bussolino, G. Camussi, M. Aglietta, P. Braquet, A. Bosia, G. Pescarmona, F. Sanavio, N. D'Urso and P. C. Marchisio,Human endothelial cells are target for platelet-activating factor I. Platelet-activating factor induces changes in cytoskeleton structures. J. Immunol.139, 2439–2446 (1987).

    PubMed  Google Scholar 

  6. P. J. Del Vecchio, A. Siflinger-Birnboim, J. M. Shephard, R. Bizios, J. A. Cooper and A. B. Malik,Endothelial monolayer permeability to macromolecules. Federation Proc.46, 2511–2515 (1987).

    Google Scholar 

  7. G. Y. Grigorian and U. S. Ryan,Platelet-activating factor effects on bovine pulmonary artery endothelial cells. Circulation Res.61, 389–395 (1987).

    PubMed  Google Scholar 

  8. I. Joris, G. Majno, E. J. Corey and R. A. Lewis,The mechanism of vascular leakage induced by leukotriene E 4. Am. J. Path.126, 19–24 (1987).

    PubMed  Google Scholar 

  9. A. M. Northover and B. J. Northover,Changes of vascular endothelial cell shape and of membrane potential in response to the ionophore A23187. Int. J. Microcirc. Clin. Exp.6, 137–148 (1987).

    PubMed  Google Scholar 

  10. A. M. Northover,The effects of indomethacin and verapamil on the shape changes of vascular endothelial cells resulting from exposure to various inflammatory agents. Agents and Actions24, 351–355 (1988).

    PubMed  Google Scholar 

  11. M. H. Malagodi, and C. Y. Chiou,Pharmacological evaluation of a new Ca 2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in smooth muscle. Eur. J. Pharmac.27, 25–33 (1974).

    Article  Google Scholar 

  12. S. J. Shetty, S. S. Rizvi and G. B. Frank,TMB-8 can block twitches without blocking high K + or caffeine induced contractures in frog's skeletal muscle. Life Sciences39, 1137–1141 (1986).

    Article  PubMed  Google Scholar 

  13. M-K, Uchida and M. Mita,Effects of Quin-2, an intracellular Ca chelator, and TMB-8, an intracellular Ca antagonist, on the short-term desensitization to histamine in guinea pig taenia caecum. Gen. Pharmac.16, 449–453 (1985).

    Google Scholar 

  14. A. W. M. Simpson, T. J. Hallam and T. J. Rink,TMB-8 inhibits secretion evoked by phorbol ester at basal cytoplasmic free calcium in quin 2-loaded platelets much more effectively than it inhibits thrombin-induced calcium mobilisation. FEBS Letters176, 139–143 (1984).

    Article  PubMed  Google Scholar 

  15. I. Kojima, K. Kojima and H. Rasmussen,Mechanism of inhibitory action of TMB-8 [8-(NN-diethylamino) octyl-3,4,5-trimethoxybenzoate] on aldosterone secretion in adrenal glomerulosa cells. Biochem. J.232, 87–92 (1985).

    PubMed  Google Scholar 

  16. A. Hassid and J-P. Oudinet,Relationship between calcium and prostaglandin synthesis in cultured vascular smooth muscle cells Prostaglandins32, 457–478 (1986).

    Article  PubMed  Google Scholar 

  17. J. V. Benventre and M. Swidler,Calcium dependency of prostaglandin E 2 production in rat glomerular mesangial cells. J. Clin. Invest.82, 168–176 (1988).

    PubMed  Google Scholar 

  18. A. M. Northover and B. J. Northover,Protection of rat atrial myocardium against electrical, mechanical and structural aspects of injury caused by exposure in vitro to conditions of simulated ischaemia. Br. J. Pharmac.94, 1207–1217 (1988).

    Google Scholar 

  19. G. J. Grega, S. W. Adamski and E. Svensjo,Is there evidence for venular large junctional gap formation in inflammation? Microcirculation, Endothelium and Lymphatics2, 211–233 (1985).

    Google Scholar 

  20. F. De Clerck, L. Van Gorp and F. Verheyen,Microvascular permeability increase in rat skin: inhibition by flunarizine, a Ca 2+ entry blocker. Blood Vessels23, 50–52 (1986).

    PubMed  Google Scholar 

  21. A. M. Northover and B. J. Northover,The effects of histamine, 5-hydroxytryptamine and bradykinin on rat mesenteric blood vessels. J. Path.98, 265–276 (1969).

    Article  PubMed  Google Scholar 

  22. E. Svensjö and G. J. Grega,Evidence for endothelial cellmediated regulation of macromolecular permeability by postcapillary venules. Federation Proc.45, 89–95 (1986).

    Google Scholar 

  23. C. G. Becker and R. L. Nachman,Contractile proteins of endothelial cells, platelets and smooth muscles. Am. J. Path.71, 1–18 (1973).

    PubMed  Google Scholar 

  24. D. Drenckhahn,Cell motility and cytoplasmic filaments in vascular endothelium. Prog. appl. Microcirc.1, 53–70 (1983).

    Google Scholar 

  25. A. K. Campbell,Calcium and cell movement, InIntracellular calcium. Its universal role as regulator, pp. 206–256. John Wiley & Sons Ltd., Chichester 1983.

    Google Scholar 

  26. T. A. Brock, R. W. Alexander and M. A. Gimbrone Jr.,Bradykinin and platelet-activating factor stimulate calcium fluxes in cultured endothelial cells. Federation Proc.43, 460 (1984).

    Google Scholar 

  27. T. A. Brock and M. A. Gimbrone Jr.,Platelet activating factor alters calcium homeostasis in cultured vascular endothelial cells. Am. J. Physiol.250, 19, H1086-H1092 (1986).

    PubMed  Google Scholar 

  28. F. Bussolino, M. Aglietta, F. Sanavio, A. Staccini, D. Lauri and G. Camussi,Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells. J. Immunol.135, 2748–2753 (1985).

    PubMed  Google Scholar 

  29. K. K. Hamilton and P. J. Sims,Changes in cytosolic Ca 2+ associated with von Willenbrand factor release in human endothelial cells exposed to histamine. J. Clin. Invest.79, 600–608 (1987).

    PubMed  Google Scholar 

  30. R. Morgan-Boyd, J. M. Stewart, R. J. Vavrek and A. Hassid,Effects of bradykinin and angiotensin II on intracellular Ca 2+ dynamics in endothelial cells. Am. J. Physiol.253, 22 C588–C598 (1987).

    Google Scholar 

  31. A. K. Campbell,The pathology and pharmacology of intracellular Ca 2+. InIntracellular calcium. Its universal role as regulator, pp 393–454, John Wiley & Sons Ltd., Chichester 1983.

    Google Scholar 

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Northover, A.M. The effects of TMB-8 on the shape changes of vascular endothelial cells resulting from exposure to various inflammatory agents. Agents and Actions 26, 367–371 (1989). https://doi.org/10.1007/BF01967303

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