Opposite effects of the catecholamines dopamine and norepinephrine on murine polyclonal B-cell activation.
The effects of dopamine (DA) and norepinephrine (NE) on polyclonal B-cell activation induced in vitro by lipopolysaccharide (LPS) and on cyclic AMP response in BALB/c mouse lymphocytes were investigated. DA at non-cytotoxic concentrations (5 x 10(-5) M and 10(-4) M) inhibited, but NE (5 x 10(-6) M to 5 x 10(-5) M) enhanced LPS-stimulated proliferation and Ig synthesis by lymphocytes from spleen, mesenteric lymph nodes and Peyer's patches. Depletion of adherent cells and T lymphocytes did not prevent the respective effects of DA and NE, and the drug effects were reproduced on nude (nu+/nu+) spleen cell proliferation and differentiation stimulated by LPS. The inhibitory effect of DA persisted even if the drug was added as late as 48 h after the mitogen. In contrast, NE was no longer stimulatory if added 2 h later than LPS. The effect of DA was blocked neither by DA1 or DA2 dopaminergic antagonists (SCH 23390 and sulpiride respectively), nor by alpha- or beta-adrenoceptor antagonists (phentolamine and propranolol respectively). Enhancement by NE was antagonized by propranolol, but not by phentolamine. Both DA and NE raised the level of cyclic AMP in unfractionated spleen cells as well as in B-enriched spleen cells but DA was less potent than NE. Pre-incubation of spleen lymphocytes with LPS for 1-24 h did not alter their cyclic AMP response to NE but it prevented the loss of sensitivity to DA after 4 or 24 h of in vitro incubation. The lysosomotropic agent chloroquine induced suppression of LPS-stimulated proliferation and Ig production with a dose-response profile similar to that of DA. Altogether, these results indicate that the catecholamines can exert opposite effects on polyclonal B-cell activation by acting directly on B lymphocytes.
Kouassi
E
E
Laboratoire d'immunologie, INSERM U80, CNRS UA 1177, UCBL, France.
Li
Y S
YS
Boukhris
W
W
Millet
I
I
Revillard
J P
JP
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D007136:Immunoglobulins / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000276:immunology
D007136:Immunoglobulins; D008070:Lipopolysaccharides; D002738:Chloroquine; D000242:Cyclic AMP; D004298:Dopamine; D009638:Norepinephrine