5-HT_1Aand β-Adrenergic Receptors Regulate Proliferation of Rat Blood Lymphocytes

Abstract

Lymphocytes possess serotonin 5-HT_1A and β-adrenergic receptors, which have been related to cell proliferation. In the present report, lymphocytes of rat blood were isolated by Ficoll-Hypaque gradients and differential adhesion to plastic. They were cultured in RPMI medium for 72 h in the presence of the mitogens lipopolysaccharide concanavalin A and anti-CD3 antibody. The latter two stimulated the proliferation of lymphocytes, but not the first. Serotonin (0.1–100 µM) was added alone or in the presence of suboptimal concentrations of concanavalin A (2 µg/ml) or anti-CD3 antibody (0.4 µg/ml). The 5-HT_1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone (0.1–100 µM) were also tested in the cultures. Serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone neither had any effect by themselves, nor modified the proliferation induced by the mitogens. Noradrenaline (25–1,000 µM) and the β-adrenergic receptor agonist, isoproterenol (5–100 µM), produced a reduction of the activation induced by concanavalin A or anti-CD3 antibody in a dose-dependent manner. Increasing serotonin concentrations reduced the inhibitory effect of noradrenaline (300 µM). Variable concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin or buspirone also reduced the inhibition produced by isoproterenol (100 µM). The antagonist of 5-HT_1A receptors, WAY-100,478 (0.1–100 µM), inhibited concanavalin A- or anti-CD3 antibody-induced proliferation. Serotonin (0.1–100 µM) impaired the inhibitory effect of the 5-HT_1A antagonist (10 µM). The inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (50–1,000 µM), decreased the stimulatory effect of concanavalin A, serotonin (0.5–100 µM) and 8-hydroxy-2-(di-n-propylamino)tetralin (1–100 µM) reverted the effect of p-chlorophenylalanine (1,000 µM). The serotonin reuptake blockers zimelidine, imipramine and clomipramine decreased concanavalin A-induced proliferation. The concentrations of serotonin and noradrenaline increased in lymphocytes cultured in the presence of concanavalin A, probably as a mechanism for modifying the final effect on proliferation. The present results indicate that 5-HT_1A receptors play a stimulatory role on rat blood lymphocytes, and they interact in a parallel and opposite manner with β-adrenergic receptors. Furthermore, endogenous serotonin is relevant in displaying its stimulatory effect.

Protein Kinase Cγ Mediates Regulation of Proliferation by the Serotonin 5-Hydroxytryptamine Receptor 2B

“…Activation of 5-HT 1A and 5-HT 2C receptors results in increased numbers of newly formed neurons in rat brain (32-34), whereas 5-HT 1A and 5-HT 1D receptors regulate mitogenesis in human small cell carcinoma of the lung (35). 5-HT 1A receptors are also involved in proliferation of T and B cells (36) and rat blood lymphocytes (37). A role for 5-HT 2B receptors in cell differentiation and proliferation has been shown in various cell types and species including mouse enteric neurons, hepatocytes, mouse cardiomyocytes, and retinal cells in Xenopus (3)(4)(5)(6)(7)38).…”

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

“…26 5-Hydroxytryptamine 1A receptors are also involved in proliferation of T cells and B cells 27 and rat blood lymphocytes. 28 A role for 5-HT 2B receptors in cell differentiation and proliferation has been shown in mouse enteric neurons 29 and hepatocytes. 6 Activation of the 5-HT 2B receptor by 5-HT also induces proliferation of mouse cardiomyocytes 30 and retinal cells in Xenopus, 31,32 indicating a conserved role for 5-HT 2B in regulating cell survival and proliferation in different species.…”

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

“…The concentration of Con A used in the cultures significantly increased proliferation as previously described [28,29]. Con A-mediated proliferation of rat blood lymphocytes is inhibited by antagonism of 5-HT 1A receptors, but it is not further elevated by agonists of this receptor [29], and Con A activation of spleen CD4+ and CD8+ T cells after 5-HT depletion is increased by 5-HT 2A receptor agonists [30].…”

“…Con A-mediated proliferation of rat blood lymphocytes is inhibited by antagonism of 5-HT 1A receptors, but it is not further elevated by agonists of this receptor [29], and Con A activation of spleen CD4+ and CD8+ T cells after 5-HT depletion is increased by 5-HT 2A receptor agonists [30]. The culture of lymphocytes in the presence of Con A increased the number of cells presenting 5-HT 7 receptors or tryptophan hydroxylase, indicating enhanced 5-HT transmission produced by lymphocyte activation.…”