Role of 5-HT2 and 5-HT7 Serotonin Receptors, and Protein Kinases C and A on Taurine Transport in Lymphocytes of Rats Treated with Fluoxetine.

Abstract

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-HT2 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-HT7 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-C16). 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-HT2 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.