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Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

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Abstract

Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

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Acknowledgments

This study is supported by National Natural Science Foundation of China (No, 31471103). We are deeply grateful to Dr. Gillian E. Knight (from the Autonomic Neuroscience Centre, University College Medical School, UK) for her kind assistance in the written English.

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Authors and Affiliations

  1. Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People’s Republic of China

    Qian Jiang, Wen-xin Li, Jia-run Sun, Tian-tian Zhu, Juan Fan, Li-hua Yu & Bei Ma

  2. Autonomic Neuroscience Centre, Royal Free Campus, University College Medical School, Rowland Hill St, London, NW3 2PF, UK

    Geoffrey Burnstock

  3. Department of Pharmacology, Melbourne University, Grattan St, Parkville, Victoria, 3010, Australia

    Geoffrey Burnstock

  4. Department of Gastroenterology, Changhai Hospital, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People’s Republic of China

    Hua Yang

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  1. Qian Jiang
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Jiang, Q., Li, Wx., Sun, Jr. et al. Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats. Purinergic Signalling 13, 105–117 (2017). https://doi.org/10.1007/s11302-016-9540-5

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  • DOI: https://doi.org/10.1007/s11302-016-9540-5

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