Fluoxetine, an antidepressant and selective serotonin reuptake inhibitor, modulates immune cells in vitro. The present study investigates the influence of pharmacological agents which acts as agonist and antagonist of serotonin receptors ex vivo over taurine transport in lymphocytes of rats treated with fluoxetine by one week. The treatment with fluoxetine increase taurine transport and the incubation with the agonist of 5-HT receptor, 1-(2,5-dimethoxy-4-iodophenyl)-​2-aminopropane (DOI) counteract this effect, and ketanserin provoked no change in fluoxetine effect. While the agonist of 5-HT receptor, 4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphth alenyl)-1-piperazinehexanamide hydrochloride (LP44) had no significant effects, however the differences between Control and Fluoxetine groups were not observed, the antagonist (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no differences. Preincubation of cells with the diacylglycerol analogue, 1-oleoyl-2-acetyl-sn-glycerol (OAG) caused inhibition of fluoxetine treatment effect but this not occurred in presence of the PKC inhibitor, 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG-C). Forskolin counteracted the effect of fluoxetine on taurine transport, since at the concentrations used, the rate of taurine transport in Fluoxetine group, returned to Control rate. No significant differences were observed with the PKA inhibitor. Although it is not possible to attribute a definitive role of 5-HT receptors in fluoxetine effect on taurine transport, its signaling might affect the function of it. Participation of PKC and PKA have an apparently relevant role in lymphocyte taurine transport.

Fluoxetine, a selective serotonin reuptake inhibitor antidepressant, modulates the mitogen-induced proliferation of lymphocytes. Lymphocytes contain taurine and express taurine transporter (TauT). Among the effects of taurine on lymphocytes are protection against oxidants and regulation of the inflammatory aspects of the immune response. Our aim was to determine the influence of fluoxetine treatment on taurine transport, and to determine the presence of TauT in the mononuclear cells of rats. Methods: Male adult Sprague-Dawley rats were treated with fluoxetine 10 mg/kg i.p. for 1, 2, and 3 weeks. The cells were obtained by density gradients. [³H]Taurine was used for transport assays. Amino acid levels were determined by high-performance liquid chromatography. Immunolabeling of CD4+, CD8+, and TauT was performed. The mRNA of TauT was evaluated by RT-PCR. Controls were included for each protocol. Results: The transport of taurine, after 1 week of treatment, was significantly augmented compared to controls. The affinity significantly increased at 1 and 2 weeks. While the percentage of CD4+ cells decreased and that of CD8+ cells increased, the percentage of TauT in CD4+ and CD8+ cells was not affected. Reduction of levels of aspartic acid, glutamic acid, threonine, alanine, glycine, and arginine occurred at 1 and 2 weeks. The taurine concentration significantly decreased after 2 and 3 weeks of treatment. The estimation of mRNA of TauT was not different. Conclusion: Taurine transport increases with fluoxetine treatment, and so this could be related to an immunomodulatory role of fluoxetine through TauT. Inhibition of serotonin reuptake might be involved in the regulation of taurine transport in mononuclear cells.