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 antidepress ants, such as clomipramine and fluoxetine (10(-8) - 10(-5) mol/l) incr ease the percentage of released serotonin in the incubation medium but have no effect on histamine release. In contrast, amitriptyline (10(- 4) mol/1) inhibits the secretion of histamine and permits that of sero tonin. The varying effects of antidepressants on the secretion of hist amine and serotonin could be explained either by a differential mechan ism of secretion of both amines from mast cells or by a selective effe ct of drugs on the reuptake of serotonin into mast cells after stimula tion by compound 48/80. These hypotheses were further investigated in our present study on rat peritoneal mast cells. Our findings suggest t hat antidepressants influence the secretion and the reuptake process o f 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/1), they inhibit the release. Additionally, mast cells are capable of removing released serotonin fr om the incubation medium. Serotonin uptake is an active process which increases with the time of incubation with exogenous serotonin and dep ends on the presence of extracellular Ca2+ and on the temperature of t he medium. Preincubation of mast cells with antidepressants inhibits t he reuptake of serotonin into mast cells and thus increases the concen tration of serotonin in the incubation medium. Since the reuptake of s erotonin is a relatively slow process, the elevation of serotonin in t he medium is evident only after longer times of incubation.