Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants.
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.
Ferjan
I
I
Department of Pharmacology, Medical Faculty, University of Ljubljana, Slovenia.
Erjavec
F
F
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000639:Amitriptyline; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D002118:Calcium; D002997:Clomipramine; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D003189:p-Methoxy-N-methylphenethylamine