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A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells

  • Authors:
    • Yuan‑Hua Liu
    • Song‑Ze Wu
    • Gang Wang
    • Ni‑Wen Huang
    • Chun‑Tao Liu
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 4121-4128
    |
    Published online on: February 5, 2015
       https://doi.org/10.3892/mmr.2015.3307
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Abstract

The persistent administration of β2‑adrenergic (β2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long‑acting β2‑adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti‑α‑smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C‑β1 (PLCβ1) were characterized by western blot analysis and the production of inositol 1,4,5‑trisphosphate (IP3) was determined using an enzyme‑linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time‑ and dose‑dependent manner, which was significantly inhibited by the β2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCβ1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol‑induced upregulated protein expression levels of M3R and PLCβ1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the β2AR‑cAMP signaling pathway, resulting in increased expression levels of PLCβ1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol‑induced bronchoprotection tolerance by suppressing the protein expression of M3R.
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Copy and paste a formatted citation
Spandidos Publications style
Liu YH, Wu SZ, Wang G, Huang NW and Liu CT: A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells. Mol Med Rep 11: 4121-4128, 2015.
APA
Liu, Y., Wu, S., Wang, G., Huang, N., & Liu, C. (2015). A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells. Molecular Medicine Reports, 11, 4121-4128. https://doi.org/10.3892/mmr.2015.3307
MLA
Liu, Y., Wu, S., Wang, G., Huang, N., Liu, C."A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells". Molecular Medicine Reports 11.6 (2015): 4121-4128.
Chicago
Liu, Y., Wu, S., Wang, G., Huang, N., Liu, C."A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells". Molecular Medicine Reports 11, no. 6 (2015): 4121-4128. https://doi.org/10.3892/mmr.2015.3307
Copy and paste a formatted citation
x
Spandidos Publications style
Liu YH, Wu SZ, Wang G, Huang NW and Liu CT: A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells. Mol Med Rep 11: 4121-4128, 2015.
APA
Liu, Y., Wu, S., Wang, G., Huang, N., & Liu, C. (2015). A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells. Molecular Medicine Reports, 11, 4121-4128. https://doi.org/10.3892/mmr.2015.3307
MLA
Liu, Y., Wu, S., Wang, G., Huang, N., Liu, C."A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells". Molecular Medicine Reports 11.6 (2015): 4121-4128.
Chicago
Liu, Y., Wu, S., Wang, G., Huang, N., Liu, C."A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype‑3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells". Molecular Medicine Reports 11, no. 6 (2015): 4121-4128. https://doi.org/10.3892/mmr.2015.3307
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