BETA-ADRENOCEPTOR-MEDIATED EFFECTS IN RAT CULTURED THYMIC EPITHELIAL-CELLS

Sympathetic nerves were visualized in sections from rat thymus by immu nostaining of tyrosine hydroxylase, the rate-limiting enzyme of catech olamine biosynthesis, and by glyoxylic acid-induced fluorescence of ca techolamines. Catecholaminergic nerve fibres were detected in close co nnection to thymic epithelial cells which therefore might be preferred target cells. To evaluate this, rat immunocytochemically defined, cul tured thymic epithelial cells were investigated for adrenoceptors and adrenergic effects. 2 In rat cultured thymic epithelial cells mRNA for beta(1)- and beta(2)-adrenoceptors was detected by reverse transcript ion-polymerase chain reaction by use of sequence-specific primers. Spe cific, saturable binding to the cultivated cells was observed with the beta-adrenoceptor agonist CGP 12177. 3 Adrenaline, noradrenaline or t he beta-adrenoceptor agonist, isoprenaline, increased intracellular ad enosine 3':5'-cyclic monophosphate (cyclic AMP) levels in cultivated t hymic epithelial cells dose-dependently about 25 fold. The pharmacolog ical properties revealed that this response was mediated by receptors for the beta(1)- and the beta(2)-subtypes. The selective beta-adrenoce ptor agonist BRL 37344 had no effect on cyclic AMP levels. The increas e in cyclic AMP was downregulated by preincubation with glucocorticoid s like dexamethasone or cortisol which also changed the relative impor tance of beta(1)-/beta(2)-adrenoceptors to the response. 4 Incubation with isoprenaline or the adenylate cyclase activator forskolin decreas ed basal and serum-stimulated proliferation of thymic epithelial cells . However, adrenergic stimulation of thymic epithelial cells did not i nduce interleukin 1 production. Since thymic epithelial cells create a microenvironment which influences the maturation and differentiation of thymocytes to T-lymphocytes, their observed capacity to respond to catecholamines provides novel evidence for the suggestion that adrener gic stimulation may interfere with the regulation of immune functions.