5-HT₇ Receptors and Tryptophan Hydroxylase in Lymphocytes of Rats: Mitogen Activation, Physical Restraint or Treatment with Reserpine

Abstract

Objectives: Serotonin (5-HT)₇ receptors in lymphocytes play a relevant role as modulators of T cell functions and might be modified by stress protocols. The aims of this work were to evaluate: (i) the presence of 5-HT₇ receptors in specific lymphocyte populations, (ii) the probable modifications of them by inflammatory stress with mitogen and (iii) the effects of physical and pharmacological stress. Methods: Blood lymphocytes were isolated by density gradients and differential adhesion to plastic. Concanavalin A (Con A) was systemically administered (500 μg/kg) or added to lymphocyte cultures (2.5 μg/ml, final volume 200 μl). Physical restraint was performed in Plexiglass boxes for 5 h per day for 5 days. Reserpine administration was 2.5 mg/kg for 3 days. Immunocytochemical labeling of CD4+, CD8+ and 5-HT₇ receptors, and also tryptophan hydroxylase cells was performed. mRNA of 5-HT₇ receptors was evaluated by RT-PCR. Controls were included for each protocol. Results: Con A treatment or culture exposure increased the number of lymphocytes expressing 5-HT₇ receptors or tryptophan hydroxylase, as compared to absence of the mitogen. Receptors were present in 12-16% of total rat lymphocytes, in ∼10% of CD4+ and in ∼5% of CD8+ cells from control rats. CD4+ decreased, and CD8+ and 5-HT₇ cells increased after physical restraint. Reserpine treatment elevated CD8+ and 5-HT₇ cells. Con A and physical restraint, but not reserpine treatment, significantly augmented 5-HT₇ receptor mRNA in lymphocytes. Conclusions: Rat lymphocytes, expressing tryptophan hydroxylase, could synthesize 5-HT, functioning as a direct autocrine modulator. The modifications of CD4+, CD8+ and 5-HT₇ receptors in lymphocytes by three stress protocols could have an impact on immune responses. In addition, the differential distribution of 5-HT₇ receptors indicates potential specific physiopathological roles.

Fluoxetine Treatment in Rats Increases the Rate of Taurine Transport in Mononuclear Cells

“…A decrease in serotonin (5-HT) concentration after treatment and its synthesis before treatment might indicate modulations in relation to lymphocyte function in people with depression [24] , since 5-HT acts as an immunomodulator that is involved in the regulation of cell activation [20] and proliferation [25,26] , and also the production of interleukin [27] . Previous results obtained in our laboratory show that rat lymphocytes express tryptophan hydroxylase, which could synthesize 5-HT and function as a direct autocrine modulator [28] . Furthermore, low numbers of peripheral-blood lymphocyte 5-HT transporters are associated with major depression.…”

“…As mentioned above, the presence of serotonin receptors in immune cells has been reported. We suggest that the 5-HT 7 and 5-HT 2 serotonin receptors are involved because the signaling of these receptors is through PKC and PKA, respectively, both of which are involved in the modulation of TauT activity [20,28] .…”

“…The 5-HT 7 receptor is the predominant 5-HT receptor expressed by naive mouse T cells and activated T cells. It is dramatically upregulated to augment early T cell activation events [20,28] . The expression of the 5-HT 2A receptor in both CD4 and CD8 T cells has been demonstrated [49] .…”

PTSD, a Disorder with an Immunological Component

“…While the mechanisms for the immune quenching have not been fully defined, peripheral blood components, such as lymphocytes, monocytes, and platelets, contain serotonin. Inhibition of serotonin transporter by SSRIs may allow increased uptake through serotonin receptors, thereby decreasing immune function ( 41 , 45 , 46 ). Alternatively, studies have suggested that SSRIs mediate the immune inhibitory effects independently of serotonin transport by depletion of calcium stores of T-cells ( 47 ).…”

Effects of Intracellular Zinc Chelator In Vivo on Taurine Transport,Taurine Concentrations and Taurine Transporter in Rat Retina Cells

“…Densitometry analysis was performed using Quantity One v.4.2.0 (Biorad) commercial software. Relative mRNA levels were expressed as densitometry intensities of the corresponding bands for the TAUT divided by those of β-actin [34].…”