Inhibition of lymphocyte activation by catecholamines: evidence for a non-classical mechanism of catecholamine action.
The effects of noradrenaline and other adrenergic agonists on lymphocyte activation were studied. Spleen and thymus cells from BALB/c mice were stimulated by mitogens and lymphocyte activation was monitored by measuring the incorporation of [methyl-3H]thymidine into DNA. Noradrenaline, adrenaline, isoproterenol and dopamine all inhibited the activation of spleen and thymus cells by concanavalin A, a T-cell specific mitogen, and the activation of spleen cells by lipopolysaccharide, a T-independent B-cell mitogen. The various catecholamines were approximately equipotent, having IC50 of approximately 10 microM. alpha-adrenergic agonists (phenylephrine, clonidine) did not inhibit lymphocyte activation. Noradrenaline, adrenaline and isoproterenol also inhibited DNA synthesis in S49 T lymphoma cells. The effects of adrenergic receptor antagonists on lymphocyte function were also studied. The inhibition of lymphocyte activation by catecholamines could not be reversed by antagonists to beta-adrenergic receptors (propranolol), alpha-adrenergic receptors (phentolamine), or dopaminergic receptors (haloperidol). Experiments with human peripheral blood leucocytes revealed that, as with murine cells, the beta-adrenergic antagonists propranolol and nadalol did not affect the catecholamine-mediated inhibition of lymphocyte activation. Although lymphocytes contain beta-adrenergic receptors that are coupled to adenylyl cyclase activity, catecholamines appear to inhibit murine lymphocyte activation by a mechanism that is independent of these or other classical adrenergic receptors.
Cook-Mills
J M
JM
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, USA.
Cohen
R L
RL
Perlman
R L
RL
Chambers
D A
DA
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017981:Receptors, Neurotransmitter / Q000819:agonists; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D018674:Adrenergic Antagonists; D002395:Catecholamines; D008070:Lipopolysaccharides; D017981:Receptors, Neurotransmitter; D003208:Concanavalin A; D004247:DNA