Purinergic Signalling

, Volume 13, Issue 1, pp 105–117 | Cite as

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

  • Qian Jiang
  • Wen-xin Li
  • Jia-run Sun
  • Tian-tian Zhu
  • Juan Fan
  • Li-hua Yu
  • Geoffrey Burnstock
  • Hua YangEmail author
  • Bei MaEmail author
Original Article


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.


Estrogen receptor β P2X3 receptor CFA TNBS Inflammation 



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.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Qian Jiang
    • 1
  • Wen-xin Li
    • 1
  • Jia-run Sun
    • 1
  • Tian-tian Zhu
    • 1
  • Juan Fan
    • 1
  • Li-hua Yu
    • 1
  • Geoffrey Burnstock
    • 2
    • 3
  • Hua Yang
    • 4
    Email author
  • Bei Ma
    • 1
    Email author
  1. 1.Department of PhysiologySecond Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Autonomic Neuroscience Centre, Royal Free CampusUniversity College Medical SchoolLondonUK
  3. 3.Department of PharmacologyMelbourne UniversityParkvilleAustralia
  4. 4.Department of Gastroenterology, Changhai HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China

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