Inflammation Research

, Volume 45, Issue 3, pp 141–144

Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants

  • I. Ferjan
  • F. Erjavec
Original Research Papers


Psychotropic agents modify the release of histamine and serotonin from rat peritoneal mast cells induced by compound 48/80. Some antidepressants, such as clomipramine and fluoxetine (10−8−10−5 mol/l), increase the percentage of released serotonin in the incubation medium but have no effect on histamine release. In contrast, amitriptyline (10−4 mol/l) inhibits the secretion of histamine and permits that of serotonin. The varying effects of antidepressants on the secretion of histamine and serotonin could be explained either by a differential mechanism of secretion of both amines from mast cells or by a selective effect of drugs on the reuptake of serotonin into mast cells after stimulation by compound 48/80. These hypotheses were further investigated in our present study on rat peritoneal mast cells.

Our findings suggest that antidepressants influence the secretion and the reuptake process of amines used. Their effects depend on the concentration of the drug. At lower concentrations, antidepressants (amitriptyline, doxepine and clomipramine) produce no effect on the secretion of the amines whereas at higher concentrations (>10−5 mol/l), they inhibit the release. Additionally, mast cells are capable of removing released serotonin from the incubation medium. Serotonin uptake is an active process which increases with the time of incubation with exogenous serotonin and depends on the presence of extracellular Ca2+ and on the temperature of the medium. Preincubation of mast cells with antidepressants inhibits the reuptake of serotonin into mast cells and thus increases the concentration of serotonin in the incubation medium. Since the reuptake of serotonin is a relatively slow process, the elevation of serotonin in the medium is evident only after longer times of incubation.

Key words

Antidepressants Histamine Serotoninuptake Secretion 


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  1. [1]
    Purcell WM, Cohen DL, Hanahoe THP. Comparison of histamine and 5-hydroxytryptamine content and secretion in rat mast cells isolated from different anatomical locations. Int Arch Allergy Appl Immunol 1989;90:382–6.Google Scholar
  2. [2]
    Irman-Florjanc T, Erjavec F. Compound 48/80 and substance P induced release of histamine and serotonin from rat peritoneal mast cells. Agents Actions 1983;13:138–41.Google Scholar
  3. [3]
    Purcell WM, Cohen DL, Hanohoe THP. Contribution of post-secretory mechanisms to the observed pattern of histamine and 5-hydroxytryptamine secretion from peritoneal mast cells in response to compound 48/80. Int Arch Allergy Appl Immunol 1989;90:387–94.Google Scholar
  4. [4]
    Purcell WM, Hanohoe THP. Differential release of histamine and 5-hydroxytryptamine from rat mast cells. The contribution of amine uptake to the apparent pattern of secretion. Agents Actions 1990;30:38–40.Google Scholar
  5. [5]
    Theoharides TC, Kops SK, Bondy PK, Askenase W. Differential release of serotonin without comparable histamine under diverse conditions in the rat mast cells. Biochem Pharmacol 1985;34:1389–98.Google Scholar
  6. [6]
    Berlin G, Enerbäck L. Non-differential inhibition of histamine and serotonin release from mast cells by amitryptiline. Agents Actions 1986;18:89–91.Google Scholar
  7. [7]
    Theoharides TC, Bondy PK, Tsalkalos ND, Askenase PW. Differential release of serotonin and histamine from mast cells. Nature 1982;297:229–31.Google Scholar
  8. [8]
    Ferjan I, Erjavec F. Contribution of serotonin reuptake to differential histamine and serotonin secretion from rat peritoneal mast cells. Inflamm Res 1995;44:28–9.Google Scholar
  9. [9]
    Knudsen T, Johansen T. Na+K+-pump activity in rat peritoneal mast cells: inhibition by extracellular calcium. Br J Pharmacol. 1989;96:773–8.Google Scholar
  10. [10]
    Shore PA, Burkhalter A, Cohen VH. A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther 1959;127:182–6Google Scholar
  11. [11]
    Erjavec F, Ferjan I. Charecteristics of histamine and serotonin release from rat mast cells induced by thymic peptides. Agents Actions 1991;33:30–2.Google Scholar
  12. [12]
    Horn AS, Trace RCAM. Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic anti-depressants into synaptosomes from serotonergic neurones in rat brain homogenates. B J Pharmacol 1974;51:399–403.Google Scholar

Copyright information

© Birkhäuser Verlag 1996

Authors and Affiliations

  • I. Ferjan
    • 1
  • F. Erjavec
    • 1
  1. 1.Department of Pharmacology, Medical FacultyUniversity of LjubljanaLjubljanaSlovenia

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