Agents and Actions

, Volume 12, Issue 4, pp 417–424 | Cite as

Histamine release from isolated rat mast cells induced by opiates: effect of sterical configuration and calcium

  • Nina Grosman
  • Steen Michael Jensen
  • Flemming Fryd Johansen
Histamine and Kinins


The stereospecificity of the action of opiates on rat mast cells was investigated by means of thel-andd-isomers levorphanol and dextrorphan. The dose-response curves for histamine release induced by the 2 drugs were of a similar shape with a maximum at 2×10−3M and a pronounced minimum at 5×10−3M. At concentrations below 5×10−3M the effect of both drugs resembled that of morphine, i.e. the release occurred rapidly and inhibition was observed with naloxone, codeine, and antimycin A. Levorphanol, dextrorphan, and the antagonist levallorphan at concentrations above 5×10−3M seemed to be toxic to mast cells.

The uptake of45Ca in connection with histamine release induced by pethidine, levorphanol, and dextrorphan was lower than that of control cells, whereas the uptake induced by morphine did not differ from that of controls. The inhibition of compound 48/80-induced histamine release by morphine was paralleled by a reduced45Ca uptake.

The time course for the inhibitory effect of preincubation with morphine was similar for the histamine release induced by morphine and by compound 48/80. Washing of the cells after preincubation with morphine was without effect on the inhibition of morphine-induced histamine release, whereas the inhibition of compound 48/80. was reduced.

The present observations with morphine and compound 48/80 support our previous impression of similarities in their mode of action, but a mechanism implying an interference by morphine with the disposition of calcium could also account for the findings. The observed antagonism between morphine and calcium resembles that of opiate receptors, but histamine release induced by opiates does not involve sterospecific opiate receptors.


Calcium Morphine Mast Cell Histamine Naloxone 
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]
    E.J. Simon andJ.M. Hiller,The opiate receptors, Ann. Rev. Pharmacol. Toxicol.18, 371–394 (1978).CrossRefGoogle Scholar
  2. [2]
    A. Beaumont andJ. Hughes,Biology of opioid peptides, Ann. Rev. Pharmacol. Toxicol.19, 245–267 (1979).CrossRefGoogle Scholar
  3. [3]
    J. Hughes, Peripheral opiate receptor mechanisms, Trends Pharmacol, Sci. TIPS2, 21–24 (1981).Google Scholar
  4. [4]
    C. Chavkin, B.M. Cox andA. Goldstein,Stereospecific opiate binding in bovine adrenal medulla, Mol. Pharmacol.15, 751–753 (1979).PubMedGoogle Scholar
  5. [5]
    L.G. Abood, H.G. Atkinson andM. MacNeil,Stereospecific opiate binding in human erythrocyte membranes and changes in heroin addicts, J. Neurosci. Res.2, 427–431 (1976).CrossRefPubMedGoogle Scholar
  6. [6]
    J. Wybran, T. Appelboom, J.-P. Famaey andA. Govaerts,Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T lymphocytes, J. Immunol.123, 1068–1070 (1979).PubMedGoogle Scholar
  7. [7]
    A. Lopker, L.G. Abood, W. Hoss andF.J. Lionetti,Stereoselective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes, Biochem. Pharmacol.29, 1361–1365 (1980).CrossRefPubMedGoogle Scholar
  8. [8]
    R.J. Gryglewski, A. Szczeklik andK. Bieron,Morphine antagonises prostaglandin E 1-mediated inhibition of human platelet aggregation, Nature256, 56–57 (1975).PubMedGoogle Scholar
  9. [9]
    A. Reches, A. Eldor, Z. Vogel andY. Salomon,Do human platelets have opiate receptors? Nature288, 382–383 (1980).CrossRefPubMedGoogle Scholar
  10. [10]
    T. Johannesson andS. Norn,The effect of morphine on the histamine contents of brain and skin in the rat, Acta Pharmacol. et Toxicol.20, 158–164 (1963).Google Scholar
  11. [11]
    H.V. Ellis, A.R. Johnson andN.C. Moran,Selective release of histamine from rat mast cells by several drugs, J. Pharmac. Exp. Ther.175, 627–631 (1970).Google Scholar
  12. [12]
    N. Grosman,Histamine release from isolated rat mast cells: effect of morphine and related drugs and their interaction with compound 48/80, Agents and Actions11, 196–203 (1981).PubMedGoogle Scholar
  13. [13]
    B. Diamant, N. Grosman, P. Stahl Skov andS. Thomle,Effect of divalent cations and metabolic energy on the anaphylactic histamine release from rat peritoneal mast cells, Int. Archs Allergy Appl. Immun.47, 412–424 (1974).Google Scholar
  14. [14]
    N. Grosman andB. Diamant,Binding of 45 calcium to isolated rat mast cells in connection with histamine release, Agents and Actions8, 338–346 (1978).PubMedGoogle Scholar
  15. [15]
    L.M. Lichtenstein andA.G. Osler,Studies on the mechanisms of hypersensitivity phenomena. IX. Histamine release from human leukocytes by ragweed pollen antigen, J. Exp. Med.120, 507–530 (1964).Google Scholar
  16. [16]
    J.C. Foreman, M.B. Hallett andJ.L. Mongar,The relationship between histamine secretion and 45 calcium uptake by mast cells, J. Physiol.271, 193–214 (1977).PubMedGoogle Scholar
  17. [17]
    D. C. Morrison andP.M. Henson, Release of mediators from mast cells and basophils induced by different stimuli. InImmediate Hypersensitivity. Modern Concepts and Developments, pp. 431–502 (Ed.M.K. Bach) Dekker, New York 1978.Google Scholar
  18. [18]
    M. Kaliner andK.F. Austen,Cyclic AMP, ATP, and reversed anaphylactic histamine release from rat mast cells, J. Immunol.112, 664–674 (1974).PubMedGoogle Scholar
  19. [19]
    L. Barr, M. Donlon, E. Chock, G.N. Catravas andM. Kaliner,Amiloride-induced histamine release from rat peritoneal mast cells (RPMCs), J. Allergy Clin. Immunol.65, 171 (1980).Google Scholar
  20. [20]
    F.A. Opmeer andJ.M. van Ree,Differential involvement of calcium in acute and chronic opioid action in the guinea-pig ileum in vitro, J. Pharmac. Exp. Ther.213, 188–195 (1980).Google Scholar
  21. [21]
    W. Kromer, E. Scheiblhuber andP. Illes,Functional antagonism by calcium of an intrinsic opioid mechanism in the guinea-pig isolated ileum, Neuropharmacol.19, 839–843 (1980).CrossRefGoogle Scholar
  22. [22]
    P. Illes, W. Zieglgänsberger andA. Herz,Calcium reverses the inhibitory action of morphine on neuroeffector transmission in the mouse vas deferens, Brain Res.191, 511–522 (1980).CrossRefPubMedGoogle Scholar
  23. [23]
    T. Kakunaga, H. Kaneto andK. Hano,Pharmacologic studies on analgesics. VII. Significance of the calcium ion in morphine analgesia, J. Pharmac. Exp. Ther.153, 134–141 (1966).Google Scholar
  24. [24]
    W.K. Schmidt andE.L. Way Hyperalgesic effects of divalent cations and antinociceptive effects of a calcium chelator in naive and morphine-dependent mice, J. Pharmac. Exp. Ther.212, 22–27 (1980).Google Scholar
  25. [25]
    M. Gothert andE. Wehking,Inhibition of Ca 2+ induced noradrenaline release from central noradrenergic neurons by morphine, Experientia36, 239–241 (1980).PubMedGoogle Scholar
  26. [26]
    G. Sanfacon, M., Houde-Depuis, R. Vanier andG. Labrecque,Calcium-induced modification of inhibition of acetylcholine release by morphine, J. Neurochem.28, 881–884 (1977).PubMedGoogle Scholar
  27. [27]
    K. Jhamandas, J. Sawynok andM. Sutak,Antagonism of morphine action on brain acetylcholine release by methylxanthines and calcium, Eur. J. Pharmac.49, 309–312 (1978).CrossRefGoogle Scholar
  28. [28]
    I.S. Sanghvi andS. Gershon,Brain calcium and morphine action, Biochem. Pharmacol.26, 1183–1185 (1977).CrossRefPubMedGoogle Scholar
  29. [29]
    D.H. Ross andH.L. Cardenas,Nerve cell calcium as a messenger for opiate and endorphin actions, Adv. Biochem. Psychopharmacol.20, 301–336 (1979).PubMedGoogle Scholar
  30. [30]
    D.B. Chapman andE.L. Way,Metal ion interactions with opiates, Ann. Rev. Pharmacol. Toxicol.,20, 553–579 (1980).CrossRefGoogle Scholar
  31. [31]
    F. Guerrero-Munoz, K.V. Cerreta, M.L. Guerrero andE.L. Way,Effect of morphine on synaptosomal Ca ++ uptake, J. Pharmac. Exp. Ther.209, 132–136 (1979).Google Scholar
  32. [32]
    F. Guerrero-Munoz, M.L. Guerrero, E.L. Way andC.H. Li,Effect of beta-endorphin on calcium uptake in the brain, Science206, 89–91 (1979).PubMedGoogle Scholar
  33. [33]
    W. Kazimierczak, M. Peret andC. Maslinski,The action of local anaesthetics on histamine release, Biochem. Pharmacol.25, 1747–1750 (1976).CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1982

Authors and Affiliations

  • Nina Grosman
    • 1
  • Steen Michael Jensen
    • 1
  • Flemming Fryd Johansen
    • 1
  1. 1.Department of PharmacologyUniversity of CopenhagenCopenhagen ØDenmark

Personalised recommendations