Role of cyclic AMP in the modulation of IgE production by the beta 2-adrenoceptor agonist, fenoterol.

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Coqueret O, Demarquay D, Lagente V

Role of cyclic AMP in the modulation of IgE production by the beta 2-adrenoceptor agonist, fenoterol.

Eur Respir J. 1996 Feb;9(2):220-5.

PubMed ID

8777955 [ View in PubMed

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Abstract

We have previously demonstrated that the beta 2-adrenoceptor agonist, salbutamol, potentiates the effect of interleukin-4 (IL-4) on immunoglobulin E (IgE) production by human peripheral blood mononuclear cells (PBMC). This study was undertaken to further define the activities of these drugs and the role of cyclic-adenosine monophosphate (cAMP) in the modulation of IgE production. Our results indicate that fenoterol (1 microM) potentiated IL-4-induced IgE production and IgE messenger ribonucleic acid (mRNA) expression. Moreover, this effect was associated with an increase in intracellular cAMP levels. The activities of this drug on IgE production were mimicked by cell permeable cAMP analogues, such as dibutyryl-cAMP (db-cAMP) (100 microM) or Sp-AMP (10 microM). The potentiating effect of fenoterol on IgE production was markedly inhibited in the presence of protein kinase A (PKA) inhibitors: H8 (10 microM) and Rp-AMP (10 microM), suggesting that its effects are likely to depend on the activation of the cAMP pathway. Additionally, the potentiating effect of fenoterol was also blocked in the presence of indomethacin. Fenoterol potentiated IL-4-induced IgE production from purified B-cells activated through their CD40 antigen. This effect was associated with an increase in cellular viability. Therefore, the activities of this drug on PBMC are likely to be mediated by the activation of another cellular type. Taken together, these results show that fenoterol potentiates the IL-4-induced IgE production via the cAMP pathway, but that this enhancement could not be explained by a direct effect on B-lymphocytes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Fenoterol	Beta-2 adrenergic receptor	Protein	Humans	Yes	Agonist	Details