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Inhibitory effects of the β 2 ‐adrenergic receptor agonist zilpaterol on the LPS‐induced production of TNF‐ α in vitro and in vivo
Author(s) -
VERHOECKX K. C. M.,
DOORNBOS R. P.,
GREEF J.,
WITKAMP R. F.,
RODENBURG R. J. T.
Publication year - 2005
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2005.00691.x
Subject(s) - agonist , chemistry , in vivo , tumor necrosis factor alpha , lipopolysaccharide , endocrinology , medicine , cyclic adenosine monophosphate , receptor , in vitro , pharmacology , biology , biochemistry , microbiology and biotechnology
In this study the anti‐inflammatory properties of zilpaterol, a β 2 ‐adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the β 2 ‐AR agonists known to date, it was noted that it was able to bind to both the β 2 ‐AR ( K i = 1.1 × 10 −6 ) and the β 1 ‐AR ( K i = 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 β 2 ‐AR, as indicated by addition of β 1 ‐ and β 2 ‐specific antagonists. The effects of zilpaterol were investigated in LPS‐treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 μ g/kg body weight reduced the TNF‐ α plasma levels. In conclusion, zilpaterol is a β 2 ‐adrenergic agonist and an inhibitor of TNF‐ α production induced by LPS both in vivo and in vitro .