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Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats

  • Authors:
    • Limei Shao
    • Yanbing Liu
    • Junhua Xiao
    • Qunying Wang
    • Fei Liu
    • Jin Ding
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang 321000, P.R. China, Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
    Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 761-770
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    Published online on: December 11, 2018
       https://doi.org/10.3892/ijmm.2018.4022
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Abstract

Increasing evidence has indicated that metabotropic glutamate receptor‑7 (mGluR7) is an important target for reducing anxiety and stress‑associated behaviours. Notably, mood disorders exhibit high levels of comorbidity with gastrointestinal dysfunction; however, the role of mGluR7 outside of the central nervous system is currently unknown. Activating mGluR7 likely increases colonic secretory function. Therefore, the present study aimed to evaluate the possible effects of mGluR7 on the visceral hypersensitivity of irritable bowel syndrome (IBS) in rats. The expression levels of mGluR7 were assessed in the colon tissues of rats with neonatal maternal separation (NMS)‑induced visceral hypersensitivity using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. In addition, the mGluR7 agonist AMN082 (3 or 10 mg/kg; i.p.) was administered 1 h prior to the visceral hypersensitivity test, and the effects of AMN082 were then observed on the nuclear factor (NF)‑κB signalling pathway. The mRNA and protein expression levels of mGluR7 were upregulated in the colon mucosa of NMS rats compared with in normal control rats. Notably, administration of AMN082 (10 mg/kg) attenuated colorectal distension (CRD)‑induced visceral hypersensitivity in NMS rats. In addition, interleukin‑10 and transforming growth factor‑β mRNA expression levels were upregulated, whereas interferon‑γ mRNA expression levels were downregulated in the NMS + AMN082 group compared with in NMS rats. The number of cluster of differentiation 3+ T cells in the intestinal mucosa and myeloperoxidase activity were decreased in NMS + AMN082 rats. Furthermore, AMN082 treatment reduced the protein expression levels of phosphorylated‑NF‑κB in the colon tissue of NMS rats. These results indicated that activation of mGluR7 may attenuate CRD‑induced visceral hypersensitivity in experimental IBS and reduce the abnormal immune cytokine response. In addition, it was suggested that the role of AMN082 in modulating the inflammatory response may be partially associated with inhibiting NF‑κB activation. These data suggested that targeting mGluR7 may be useful in the treatment of stress‑associated IBS.
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Copy and paste a formatted citation
Spandidos Publications style
Shao L, Liu Y, Xiao J, Wang Q, Liu F and Ding J: Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats. Int J Mol Med 43: 761-770, 2019.
APA
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., & Ding, J. (2019). Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats. International Journal of Molecular Medicine, 43, 761-770. https://doi.org/10.3892/ijmm.2018.4022
MLA
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., Ding, J."Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats". International Journal of Molecular Medicine 43.2 (2019): 761-770.
Chicago
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., Ding, J."Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats". International Journal of Molecular Medicine 43, no. 2 (2019): 761-770. https://doi.org/10.3892/ijmm.2018.4022
Copy and paste a formatted citation
x
Spandidos Publications style
Shao L, Liu Y, Xiao J, Wang Q, Liu F and Ding J: Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats. Int J Mol Med 43: 761-770, 2019.
APA
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., & Ding, J. (2019). Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats. International Journal of Molecular Medicine, 43, 761-770. https://doi.org/10.3892/ijmm.2018.4022
MLA
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., Ding, J."Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats". International Journal of Molecular Medicine 43.2 (2019): 761-770.
Chicago
Shao, L., Liu, Y., Xiao, J., Wang, Q., Liu, F., Ding, J."Activating metabotropic glutamate receptor‑7 attenuates visceral hypersensitivity in neonatal maternally separated rats". International Journal of Molecular Medicine 43, no. 2 (2019): 761-770. https://doi.org/10.3892/ijmm.2018.4022
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