Abstract |
In this study the anti-inflammatory properties of zilpaterol, a beta2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the beta2-AR agonists known to date, it was noted that it was able to bind to both the beta2-AR (Ki = 1.1 x 10(-6)) and the beta1-AR (Ki = 1.0 x 10(-5)). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3',5'-cyclic monophosphate (cAMP) and tumor necrosis factor alpha ( TNF-alpha) were investigated. Zilpaterol inhibited TNF-alpha release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-alpha release and induction of cAMP production was mainly mediated via the beta2-AR, as indicated by addition of beta1- and beta2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 microg/kg body weight reduced the TNF-alpha plasma levels. In conclusion, zilpaterol is a beta2-adrenergic agonist and an inhibitor of TNF-alpha production induced by LPS both in vivo and in vitro.
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Authors | K C M Verhoeckx, R P Doornbos, J van der Greef, R F Witkamp, R J T Rodenburg |
Journal | Journal of veterinary pharmacology and therapeutics
(J Vet Pharmacol Ther)
Vol. 28
Issue 6
Pg. 531-7
(Dec 2005)
ISSN: 0140-7783 [Print] England |
PMID | 16343285
(Publication Type: Journal Article)
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Chemical References |
- Adrenergic beta-Agonists
- Immunologic Factors
- Lipopolysaccharides
- Trimethylsilyl Compounds
- Tumor Necrosis Factor-alpha
- Zilpaterol
- Cyclic AMP
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Topics |
- Adrenergic beta-Agonists
(administration & dosage, pharmacology)
- Animals
- Cattle
- Cyclic AMP
(metabolism)
- Dose-Response Relationship, Drug
- Escherichia coli
- Humans
- Immunologic Factors
(administration & dosage, pharmacology)
- Lipopolysaccharides
- Macrophage Activation
(drug effects)
- Male
- Rats
- Rats, Wistar
- Trimethylsilyl Compounds
(administration & dosage, pharmacology)
- Tumor Necrosis Factor-alpha
(drug effects, metabolism)
- U937 Cells
(drug effects, metabolism)
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