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.

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