eprintid: 1529187 rev_number: 26 eprint_status: archive userid: 608 dir: disk0/01/52/91/87 datestamp: 2016-11-22 13:45:20 lastmod: 2021-10-06 22:15:51 status_changed: 2016-11-22 13:45:20 type: article metadata_visibility: show creators_name: Jiang, Q creators_name: Li, WX creators_name: Sun, JR creators_name: Zhu, TT creators_name: Fan, J creators_name: Yu, LH creators_name: Burnstock, G creators_name: Yang, H creators_name: Ma, B title: Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 keywords: CFA, Estrogen receptor β, Inflammation, P2X3 receptor, TNBS note: © Springer Science+Business Media Dordrecht 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s11302-016-9540-5 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. date: 2017-03 date_type: published official_url: http://doi.org/10.1007/s11302-016-9540-5 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1192062 doi: 10.1007/s11302-016-9540-5 pii: 10.1007/s11302-016-9540-5 lyricists_name: Burnstock, Geoffrey lyricists_id: GBURN46 actors_name: Burnstock, Geoffrey actors_id: GBURN46 actors_role: owner full_text_status: public publication: Purinergic Signalling volume: 13 number: 1 pagerange: 105-117 event_location: Netherlands issn: 1573-9546 citation: Jiang, Q; Li, WX; Sun, JR; Zhu, TT; Fan, J; Yu, LH; Burnstock, G; ... Ma, B; + view all <#> Jiang, Q; Li, WX; Sun, JR; Zhu, TT; Fan, J; Yu, LH; Burnstock, G; Yang, H; Ma, B; - view fewer <#> (2017) Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats. Purinergic Signalling , 13 (1) pp. 105-117. 10.1007/s11302-016-9540-5 <https://doi.org/10.1007/s11302-016-9540-5>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1529187/1/burnstock_PS-151202%28GEK%29.pdf