5-HT1A and beta-adrenergic receptors regulate proliferation of rat blood lymphocytes.
Lymphocytes possess serotonin 5-HT(1A) and beta-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 microM) was added alone or in the presence of suboptimal concentrations of concanavalin A (2 microg/ml) or anti-CD3 antibody (0.4 microg/ml). The 5-HT(1A) receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone (0.1-100 microM) 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 microM) and the beta-adrenergic receptor agonist, isoproterenol (5-100 microM), 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 microM). Variable concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin or buspirone also reduced the inhibition produced by isoproterenol (100 microM). The antagonist of 5-HT(1A) receptors, WAY-100,478 (0.1-100 microM), inhibited concanavalin A- or anti-CD3 antibody-induced proliferation. Serotonin (0.1-100 microM) impaired the inhibitory effect of the 5-HT(1A) antagonist (10 microM). The inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (50-1,000 microM), decreased the stimulatory effect of concanavalin A, serotonin (0.5-100 microM) and 8-hydroxy-2-(di-n-propylamino)tetralin (1-100 microM) reverted the effect of p-chlorophenylalanine (1,000 microM). 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 beta-adrenergic receptors. Furthermore, endogenous serotonin is relevant in displaying its stimulatory effect.
Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Telésfora
T
Sempere
Mary
M
Urbina
Lucimey
L
Lima
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012701:Serotonin / Q000097:blood / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000494:pharmacology; D013566:Sympathomimetics / Q000097:blood / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000906:Antibodies; D017252:CD3 Complex; D008070:Lipopolysaccharides; D011943:Receptors, Adrenergic, beta; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013566:Sympathomimetics; D003208:Concanavalin A; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007545:Isoproterenol; D010134:Fenclonine; D009638:Norepinephrine