Inhibitory effects of the β2‐adrenergic receptor agonist zilpaterol on the LPS‐induced production of TNF‐α in vitro and in vivo
- 15 November 2005
- journal article
- Published by Wiley in Journal of Veterinary Pharmacology and Therapeutics
- Vol. 28 (6), 531-537
- https://doi.org/10.1111/j.1365-2885.2005.00691.x
Abstract
In this study the anti-inflammatory properties of zilpaterol, a β2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the β2-AR agonists known to date, it was noted that it was able to bind to both the β2-AR (Ki = 1.1 × 10−6) and the β1-AR (Ki = 1.0 × 10−5). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3′,5′-cyclic monophosphate (cAMP) and tumor necrosis factor alpha (TNF-α) were investigated. Zilpaterol inhibited TNF-α release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-α release and induction of cAMP production was mainly mediated via the β2-AR, as indicated by addition of β1- and β2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 μg/kg body weight reduced the TNF-α plasma levels. In conclusion, zilpaterol is a β2-adrenergic agonist and an inhibitor of TNF-α production induced by LPS both in vivo and in vitro.Keywords
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