Abstract
We predicted that zilpaterol hydrochloride (ZH), a β-adrenergic receptor (AR) agonist, would depress mRNA and protein abundance of β-AR in bovine satellite cells. We also predicted that ZH would decrease total lipid synthesis in bovine adipose tissue. Bovine satellite cells isolated from the semimembranosus muscle were plated on tissue culture plates coated with reduced growth factor matrigel or collagen. Real-time quantitative PCR was used to measure specific gene expression after 48 h of ZH exposure in proliferating satellite cells and fused myoblasts. There was no effect of ZH dose on [(3)H]thymidine incorporation into DNA in proliferating myoblasts. Zilpaterol hydrochloride at 1 µM decreased (P < 0.05) β1-AR mRNA, and 0.01 and 1 µM ZH decreased (P < 0.05) β2-AR and β3-AR mRNA in myoblasts. The expression of IGF-I mRNA tended to increase (P = 0.07) with 1 µM ZH. There was no effect (P > 0.10) of ZH on the β-AR or IGF-I gene expression in fused myotube cultures at 192 h or on fusion percentage. The β2-AR antagonist ICI-118, 551 at 0.1 µM attenuated (P < 0.05) the effect of 0.1 µM ZH to reduce expression of β1- and β2-AR mRNA. The combination of 0.01 µM ZH and 0.1 µM ICI-118, 551 caused an increase (P < 0.05) in β1-AR gene expression. There was no effect (P > 0.10) of ICI-118, 551 or ZH on β3-AR or IGF-I. Western blot analysis revealed that the protein content of β2-AR in ZH-treated myotube cultures decreased (P < 0.05) relative to control. Total lipid synthesis from acetate was increased by ZH in bovine subcutaneous adipose tissue explants in the absence of theophylline but was decreased by ZH when theophylline was included in the incubation medium. These data indicate that ZH alters mRNA and protein concentrations of β-AR in satellite cell cultures, which in turn could affect responsiveness of cells to prolonged ZH exposure in vivo. Similar to other β-adrenergic agonists, ZH had only modest effects on lipid metabolism in adipose tissue explants.
Highlights
Zilpaterol hydrochloride (ZH) is an orally active β-adrenergic receptor (AR) agonist approved for use in feedlot cattle in the United States (Delmore et al, 2010)
The total weight and protein content of the muscles from the hind limb of the lambs was increased by 30% during the 3-wk administration of cimaterol, suggesting that an increase in satellite cell proliferation was not necessary to support the β-agonist induced muscle hypertrophy
In contrast to our data, Grant et al (1990) observed an increase in cell proliferation in muscle satellite cells isolated from chick breast muscle with ractopamine treatment; there was no effect on the fusion of those cells into the muscle fiber
Summary
Zilpaterol hydrochloride (ZH) is an orally active β-adrenergic receptor (AR) agonist approved for use in feedlot cattle in the United States (Delmore et al, 2010). Administration of ZH to feedlot steers and heifers the last 20 to 40 d on feed increased ADG, ribeye area, and dressing percentage and improved feed efficiency and carcass yield grade (Beckett et al, 2009; Montgomery et al, 2009; Baxa et al, 2010). Zilpaterol hydrochloride elicits a response through binding to β-AR, which are membrane-bound receptors located on most mammalian cells (Strosberg et al, 1993; Mills and Mersmann, 1995). The activation of protein kinase A, as elicited by β-adrenergic agonist (β-AA), is responsible for changes in protein synthesis and degradation, in skeletal muscle (Mersmann, 1998), and ZH putatively works to increase muscle growth via binding to the β-AR. The treatment of ZH induced fast glycolytic fiber types such as myosin heavy chain IIX rather than slow oxidative fiber types such as myosin heavy chain I (Baxa et al, 2010).
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