Mechanisms of Action of Anesthetics on Inositol Phospholipid Hydrolysis in Vascular Endothelial Cells and Rat Basophilic Leukemia Cells in Tissue Culture

  • A. Robinson-White
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 301)


The different classes of anesthetics (i.e., barbiturates, local anesthetics, and volatile anesthetics) have been shown to exert separate patterns of effects on the vasculature.1–7 Theories as to the mechanism(s) of these effects suggest that anesthetics act either by the specific alteration of membrane proteins, or in a non-specific manner on membrane proteins, through the perturbation of membrane lipids.8–10 Although no suggestion as to the degree of specificity of the anesthetics on membrane proteins has been offered, they are thought to act on cellular biochemical processes by alteration of ion fluxes (in particular Ca2+)1,11–13 in the vascular smooth muscle cell.1 Our recent studies have shown that anesthetics can alter one Ca2+-mediated cellular pathway in vascular endothelial cells, the phosphatidylinositol pathway (inositol phospholipid hydrolysis).14


Phosphatidic Acid Inositol Phosphate Volatile Anesthetic Inositol Triphosphate Inositol Phospholipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. M. Altura, B. J. Altura, A. Carclla, P. D. M. V. Turlapathy and J. Weinberg, Vascular smooth muscle and general anesthetics, Fed Proc 39:1584 (1980).PubMedGoogle Scholar
  2. 2.
    R. D. Miller, “Anesthesia,” Churchill Livingstone, New York (1981).Google Scholar
  3. 3.
    N. T. Muth and P. C. Smith, Circulatory effects of modern inhalation anesthetic agents”, in: “Handbook of Experimental Pharmacology,” M. B. Clenoweth, ed., Springer-Verlag, Berlin, (1972).Google Scholar
  4. 4.
    D. E. Longnecker and P. D. Harris, Dilation of small arteries and veins in the bat during halothane anesthetics, Anesthesioi 37:423 (1971).CrossRefGoogle Scholar
  5. 5.
    P. D. Harris, L. F. Hodoval and D. E. Longnecker. Quantitative analysis of microvascular diameters during pentobarbital and thiopental anesthesia in the bat, Anesthesioi 35:337 (1972).CrossRefGoogle Scholar
  6. 6.
    J. E. Faber, P. D. Harris and D. L. Wiegman, Anesthetic depression of microcirculation, central hemodynamics, and respiration in decerebrate ratsam J Physiol 243:H837 (1982).Google Scholar
  7. 7.
    B. M. Altura and B. T. Altura, Effects of local anesthetics, antihistamines, and glucocorticoids on peripheral blood flow in vascular smooth muscle, Anesthesioi 41:197 (1974).CrossRefGoogle Scholar
  8. 8.
    P. Seeman, The membrane actions of anesthetics and tranquilizers, Pharmacol Rev 24:583 (1972).PubMedGoogle Scholar
  9. 9.
    F. S. Labella, Is there a general anesthesia receptor? Can J Physiol Pharmacol 59: 432 (1981).PubMedGoogle Scholar
  10. 10.
    P. R. Andrews and L. C. Mark, Structural specificity of barbiturates and related drugs, Anesthesioi 57:314, (1982).CrossRefGoogle Scholar
  11. 11.
    E. M. Vaughn Williams, A classification of anti-arrhythmic actions reassessed after a decade of new drugs, J Clin Pharmacol 24:129 (1984).Google Scholar
  12. 12.
    C. F. Stamer, Theoretical characterization of ion channel blockade: Competitive binding to periodically accessible receptors, Biophys J 52:405 (1987).CrossRefGoogle Scholar
  13. 13.
    D. Kenny, L. R. Pelc, H. L. Brooks, J. P. Kampine, W. T. Schmeling and D. C. Warlticr, Calcium channel modulation of α1 and α2-adrenergic pressor responses in conscious and anesthetized dogs, Anesthesioi 72:874 (1990).CrossRefGoogle Scholar
  14. 14.
    A. J. Robinson-White, S. M. Muldoon and F. C. Robinson, Inhibition of inositol phospholipid hydrolysis in endothelial cells by pentobarbital, Eur J Pharmacol 172:291 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    M. J. Berridge, Inositol triphosphate and diacylglycerol as second messengers, Biochem J 220:345 (1984).PubMedGoogle Scholar
  16. 16.
    M. J. Berridge and R. F. Irvine, Inositol triphosphate a novel second messenger in cellular signal transduction, Nature 312:315 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    S. Cockcroft and B. D. Gomperts, Role of guanine nucleotide binding protein in the activation of phosphoinositide phosphodiesterase, Nature 314:534 (1985).PubMedCrossRefGoogle Scholar
  18. 18.
    C. D. Smith, C. C. Cox and R. Snyderman, Receptor-coupled activation of phosphoinositide-specific phospholipase C. by an N protein, Science 232:97 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    Y. Nishizuka, The role of protein kinase C. in cell surface signal transduction and tumor promotion, Nature 308:693 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    R. F. Furchgott and J. V. Zawadzki, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature 288:373 (1980).PubMedCrossRefGoogle Scholar
  21. 21.
    R. F. O’Brien, R. J. Robbins and I. V. McMurty, Endothelial cells in culture produce a vasoconstrictor substance, J Cell Physiol 132:263 (1980).CrossRefGoogle Scholar
  22. 22.
    M. Yanagsawa, H. Karihara, S. Kimara, Y. Tomobe, M. Kobayashi, M. Mitsui, Y. Goto and T. Maski, A novel potent vasoconstrictor peptide produced by vascular endothelial cells, Nature 332:411 (1988).CrossRefGoogle Scholar
  23. 23.
    S. M. Schwartz, Selection and characterization of bovine aortic endothelial cells, In Vitro 14:966 (1986).CrossRefGoogle Scholar
  24. 24.
    E. L. Barsumian, C. Sersky, M. G. Petrino and R. P. Siraganian, IgE-induced histamine release from rat basophilic leukemia lines: Isolation of releasing and non-releasing clones. Eur J Immunol 11:317 (1981).PubMedCrossRefGoogle Scholar
  25. 25.
    H. Ali, J. R. Cunha-Melo and M. A. Beaven, Receptor-mediated release of inositol 1,4-bisphosphate in rat basophilic leukemia RBL-2H3 cells permeabilized with streptolysin O. Biochem Biophys Acta 1010:88 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    F. J. Leonetti, S. M. Hunt, P. S. Lin, S. R. Kurtz and C. R. Valeri, Preservation of human granulocytes obtained by counterflow centrifugation, Transfusion 17:465 (1977).CrossRefGoogle Scholar
  27. 27.
    S. M. Muldoon, P. M. Vanhoutte, R. R. Lorenz and R. A. Van Dyke, Venomotor changes are caused by halothane acting on the sympathetic nerves, Anesthesiol 43:41 (1975).CrossRefGoogle Scholar
  28. 28.
    A. J. Robinson-White, S. M. Muldoon, L. Elson and D. M. Collado-Escobar, Evidence that barbiturates inhibit antigen-induced responses through interactions with a GTP-binding protein in rat basophilic leukemia (RBL-2H3) cells, Anesthesiol 72:996 (1990).CrossRefGoogle Scholar
  29. 29.
    H. Ali, J. R. Cunha-Melo, W. Saul and M. A. Beaven, Activation of phospholipase C. via adenosine receptors provides synergistic signals for secretion in antigen-simulated RBL-2H3 cells, J Biol Chem 265:745 (1990).PubMedGoogle Scholar
  30. 30.
    M. A. Beaven, J. P. Moore, G. A. Smith, T. R. Hasketh and J. C. Metcalfe, The calcium signal and phosphatidylinositol breakdown in 2H3 cells, J Biol Chem 259:7137 (1984).PubMedGoogle Scholar
  31. 31.
    H. Ali, D. M. Collado-Escobar and M. A. Beaven, The rise in concentration of free Ca2+ and of pH provide sequential synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells, J Immunol 143:2626 (1989).PubMedGoogle Scholar
  32. 32.
    R. J. Lefkowitz, M. G. Caron and G. L. Stetes, Mechanisms of membrane-receptor regulation. Biochemical, physiological, and clinical insights derived from studies of the adrcnergic receptor, New Engl J Med 310:1570 (1984).PubMedCrossRefGoogle Scholar
  33. 33.
    A. G. Gilman, G-Proteins: Transducers of receptor-generated signals, Ann Rev Biochem 56:60 (1987).CrossRefGoogle Scholar
  34. 34.
    V. Narasimihan, D. Holowky, C. Fewtrell and B. Baird, Cholera toxin increases the rate of antigen-stimulated calcium influx in rat basophilic leukemia cells, J Biol Chem 263:19626 (1988).Google Scholar
  35. 35.
    H. Ali, D. M. Collado-Escobar, J. R. Cunha-Melo, H. M. S. Gonzago, F. L. Huang, K-P. Haung and M. A. Beaven, Studies of protein kinase C. in the rat basophilic leukemia (RBL-2H3) cell reveals that antigen-induced signals are not mimicked by the actions of phorbol myristate acetate Ca2+ ionophore, J Immunol 143:2617 (1989).PubMedGoogle Scholar
  36. 36.
    K. Macyama, R. J. Hohman, H. Metzger and M. A. Beaven, Quantitative relationships between aggregation of IgE receptors, generation of intraccllular signals, and histaminc secretion in rat basophilic leukemia (2H3) cells, J Biol Chem 261:2583–2592 (1986).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • A. Robinson-White

There are no affiliations available

Personalised recommendations