Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fenoterol, a beta 2-adrenergic agonist recently introduced to treat asthmatic disorders, inhibits antigen-induced histamine release from human basophil leukocytes and lung mast cells in a dose-dependent fashion. The dose-response inhibition curve is paralleled by a fenoterol-induced increase in the cAMP levels of human leukocyte preparations. The relationship between the effect of fenoterol and cAMP level is supported by the finding that the beta 2-adrenergic agonist only inhibits the first stage of antigen-induced histamine release and not the release caused by the Ca2+ ionophore, A23187. Propranolol, a competitive antagonist of beta 2-adrenergic receptor, blocks the inhibition of release and the cAMP accumulation caused by fenoterol. Finally, theophylline, a cAMP phosphodiesterase inhibitor, synergistically potentiates the inhibitory effect of fenoterol on histamine release and the accumulation of cAMP. These data suggest that fenoterol may modulate the in vivo release of the mediators of immediate hypersensitivity reactions via the activation of beta 2-adrenergic receptor linked to adenylate cyclase on human basophils and mast cells.
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PMID:Inhibition of IgE-mediated histamine release from human basophils and mast cells by fenoterol. 620 44

Chronic exposure of human isolated bronchi to beta2-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. 5'-Cyclic adenosine monophosphate (cAMP) pathways are involved in fenoterol-induced hyperresponsiveness. The present study investigated whether chronic elevation of intracellular cAMP by other pathways than beta2-adrenoceptor stimulation provokes bronchial hyperresponsiveness. Samples from eighteen human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C), or, under similar conditions, were incubated with a selective type-3 phosphodiesterase inhibitor (1 microM siguazodan), two selective type-4 phosphodiesterase inhibitors (0.1 microM rolipram and 0.1 microM cilomilast), a combination of fenoterol and rolipram (0.1 microM each) or of fenoterol and cilomilast (0.1 microM each). Rolipram and cilomilast, but not siguazodan, induced hyperresponsiveness (p < 0.01 and p < 0.05 vs. paired controls, respectively) similar to the fenoterol effect. Fenoterol-induced bronchial hyperresponsiveness was significantly enhanced by coincubation with cilomilast (p < 0.05 vs. fenoterol alone) but not with rolipram. Our results suggest that prolonged activation of intracellular cAMP through phosphodiesterase 4 inhibition induces hyperresponsiveness to ET-1 in human isolated bronchi. However, differences in subcellular localization of phosphodiesterase 4 may provoke divergent responsiveness patterns when human bronchi are continuously exposed to selective phosphodiesterase inhibitors with or without beta2-adrenergic agonists.
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PMID:Phosphodiesterase 4 inhibitors modulate beta2-adrenoceptor agonist-induced human airway hyperresponsiveness. 1682 Jan 75