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Br J Pharmacol. Apr 1997; 120(8): 1401–1408.
PMCID: PMC1564613

β-Adrenoceptor-mediated effects in rat cultured thymic epithelial cells

Abstract

  1. Sympathetic nerves were visualized in sections from rat thymus by immunostaining of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, and by glyoxylic acid-induced fluorescence of catecholamines. Catecholaminergic nerve fibres were detected in close connection to thymic epithelial cells which therefore might be preferred target cells. To evaluate this, rat immunocytochemically defined, cultured thymic epithelial cells were investigated for adrenoceptors and adrenergic effects.
  2. In rat cultured thymic epithelial cells mRNA for β1- and β2-adrenoceptors was detected by reverse transcription-polymerase chain reaction by use of sequence-specific primers. Specific, saturable binding to the cultivated cells was observed with the β-adrenoceptor agonist CGP 12177.
  3. Adrenaline, noradrenaline or the β-adrenoceptor agonist, isoprenaline, increased intracellular adenosine 3′ : 5′-cyclic monophosphate (cyclic AMP) levels in cultivated thymic epithelial cells dose-dependently about 25 fold. The pharmacological properties revealed that this response was mediated by receptors of the β1- and the β2-subtypes. The selective β3-adrenoceptor agonist BRL 37344 had no effect on cyclic AMP levels. The increase in cyclic AMP was downregulated by preincubation with glucocorticoids like dexamethasone or cortisol which also changed the relative importance of β1-/β2-adrenoceptors to the response.
  4. Incubation with isoprenaline or the adenylate cyclase activator forskolin decreased basal and serum-stimulated proliferation of thymic epithelial cells. However, adrenergic stimulation of thymic epithelial cells did not induce 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 adrenergic stimulation may interfere with the regulation of immune functions.
Keywords: Adrenergic nerves, β-adrenoceptors, CGP 12177, cyclic AMP, proliferation, neuroimmunology, thymus, thymic epithelial cells, glucocorticoids

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