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Agents and Actions

, Volume 12, Issue 4, pp 431–437 | Cite as

Anthracycline-induced histamine release from rat mast cells

  • E. A. Riegel
  • M. Kaliner
  • A. N. El-Hage
  • V. J. Ferrans
  • O. Kawanami
  • E. H. Herman
Histamine and Kinins

Abstract

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminaryin vitro experiments indicated that doxorubicin (10−6 to 2.5×10−4M), in contrast to compound 48/80 and the calcium inophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. Inin vivo experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10−5 to 3.3×10−3M revealed that all caused histamine release, with 10−3M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5×10−6M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent.

The results indicate thatin vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat skin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparationsin vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.

Keywords

Mast Cell Histamine Doxorubicin Vascular Permeability A23187 
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.

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References

  1. [1]
    R.H. Blum andS.K. Carter,Adriamycin: A new anticancer drug with significant clinical activity, Ann. Intern. Med.80, 249–259 (1974).PubMedGoogle Scholar
  2. [2]
    E. Etcubanas andJ.R. Wilbur,Uncommon side effects of adriamycin (NSC 123127), Cancer Chemother. Rep.58, 756–757 (1974).Google Scholar
  3. [3]
    E. Herman, R. Mhatre, I.P. Lee, J. Vick andV.S. Waravdekar,A comparison of cardiovascular actions of daunomycin, adriamycin, and N-acetyldaunomycin in hamsters and monkeys, Pharmacology6, 230–241 (1971).PubMedGoogle Scholar
  4. [4]
    E.H. Herman, R. Young andS. Krop,Doxorubicin-induced hypotension in the beagle dog, Agents and Actions8, 551–557 (1978).PubMedGoogle Scholar
  5. [5]
    E.H. Herman andR.S.K. Young,Acute cardiovascular alterations induced by low doses of adriamycin, rubidazone and daunorubicin in the anesthetized beagle dog, Cancer Treatment Rep.63, 1771–1779 (1979).Google Scholar
  6. [6]
    T.J. Sullivan, K.L. Parker, W. Stenson andC.W. Parker,Modulation of cyclic AMP in purified rat mast cells. I. Responses to pharmacologic, metabolic and physical stimuli, J. Immun.114, 1473–1479 (1975).PubMedGoogle Scholar
  7. [7]
    D.C. Morrison, J.F. Roser, P.M. Henson andC.G. Cochrane,Activation of rat mast cells by low molecular weight stimuli, J. Immun.112 573–582 (1974).PubMedGoogle Scholar
  8. [8]
    D.W. Fawcett,Cytological and pharmacological observations on the release of histamine by mast cells, J. Exp. Med.100, 217–224 (1954).PubMedGoogle Scholar
  9. [9]
    M.A. Beaven, A. Robinson-White, N.B. Roderick andG. Kauffman,The demonstration of histamine release in clinical conditions: A review of past and present assay procedures, Klin. Wschr. (in press), (1982).Google Scholar
  10. [10]
    R.E. Shaff andM.A. Beaven,Increased sensitivity of the enzymatic isotopic assay of histamine: Measurement of histamine in plasma and serum, Analyt. Biochem.94, 425–430 (1979).CrossRefPubMedGoogle Scholar
  11. [11]
    J.W. Combs,Maturation of rat mast cells. An electron microscope study, J. Cell Biol.31, 563–575 (1966).CrossRefPubMedGoogle Scholar
  12. [12]
    L.M. Lichtenstein, J.C. Foreman, M.C. Conroy, G. Marone andH.H. Newball, Differences between histamine release from rat mast cells and human basophils and mast cells. InThe Mast Cell. Its Role in Health and Disease, pp. 83–95. (EdsJ. Pepys andA.M. Edwards) Pitman Medical, Tunbridge Wells 1979.Google Scholar
  13. [13]
    R.B. Weiss andS. Bruno,Hypersensitivity reactions to cancer chemotherapeutic agents, Ann. Intern. Med.94, 66–72 (1981).PubMedGoogle Scholar
  14. [14]
    C.L. Jacquillat, M. Weil, M.F. Gemon-Auclerc, V. Izarel, A. Bussel, M. Boiron andJ. Bernard,Clinical study of rubidazone (22 050 R.P.), a new daunorubicin-derived compound, in 170 patients with acute leukemias and other malignancies, Cancer37, 653–659 (1976).PubMedGoogle Scholar
  15. [15]
    R.S. Benjamin, M.J. Keating, K.D. Swenerton, S. Legha andK.B. McCredle,Clinical studies with rubidazone, Cancer Treat. Rep.63, 925–929 (1979).PubMedGoogle Scholar
  16. [16]
    N.R. Bachur, M. Steele, W.D. Meriwether andR.C. Hildebrand,Cellular pharmacodynamics of several anthracycline antibiotics, J. Med. Chem.19 (S), 651–654 (1970).CrossRefGoogle Scholar
  17. [17]
    P. Rohlich, P. Anderson andB. Uvnas,Electron microscope observations on compound 48/80-induced degranulation in rat mast cells. Evidence for sequential exocytosis of storage granules, J. Cell Biol.51, 465–483 (1971).PubMedGoogle Scholar
  18. [18]
    D. Lagunoff,Membrane fusion during mast cell secretion, J. Cell Biol.57, 252–259 (1973).CrossRefPubMedGoogle Scholar
  19. [19]
    E.Y. Chi, D. Lagunoff andJ.K. Koehler,Freezefracture study of mast cell secretion, Proc. Natn. Acad. Sci. USA73, 2823–2827 (1976).Google Scholar
  20. [20]
    S.J. Burwen andB.H. Satir,Plasma membrane folds on the mast cell surface and their relationship to secretory activity, J. Cell Biol.74 690–697 (1977).CrossRefPubMedGoogle Scholar
  21. [21]
    D. Lawson, M.C. Raff, B. Gomperts C. Fewtrell andN.B. Gilula,Molecular events during membrane fusion. A study of exocytosis in rat peritoneal mast cells, J. Cell Biol.72, 242–259 (1977).PubMedGoogle Scholar
  22. [22]
    C. Prottey andT.F. Ferguson,The effect of surfactants upon rat peritoneal mast cells in vitro, Fd. Cosmet. Toxicol.14, 425–430 (1976).CrossRefGoogle Scholar
  23. [23]
    A.R. Johnson andN.C. Moran,Selective release of histamine from rat mast cells by compound 48/80 and antigen, Am. J. Physiol.216, 453–459 (1969).PubMedGoogle Scholar
  24. [24]
    W.D.M. Paton,Histamine release by compounds of simple chemical structure, Pharmac. Rev.9, 269–328 (1957).Google Scholar
  25. [25]
    A. Goth, H.R. Adams andM. Knoohuizen,Phosphatidylserine: Selective enhancer of histamine release, Science173, 1034–1035 (1971).PubMedGoogle Scholar
  26. [26]
    A. Sydbom andB. Uvnas,Potentiation of anaphylactic histamine release from isolated rat pleural mast cells by rat serum phospholipids, Acta Physiol. Scand.97, 222–232 (1976).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1982

Authors and Affiliations

  • E. A. Riegel
    • 1
  • M. Kaliner
    • 2
  • A. N. El-Hage
    • 1
  • V. J. Ferrans
    • 3
  • O. Kawanami
    • 3
  • E. H. Herman
    • 1
  1. 1.Division of Drug Biology, Bureau of DrugsFood and Drug AdministrationWashington DC
  2. 2.National Institutes of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA
  3. 3.National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA

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