Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats.
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.
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Qian
Q
Jiang
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Wen-Xin
WX
Li
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Jia-Run
JR
Sun
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Tian-Tian
TT
Zhu
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Juan
J
Fan
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China.
Li-Hua
LH
Yu
Autonomic Neuroscience Centre, Royal Free Campus, University College Medical School, Rowland Hill St, London, NW3 2PF, UK.|Department of Pharmacology, Melbourne University, Grattan St, Parkville, Victoria, 3010, Australia.
Geoffrey
G
Burnstock
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China. Yanghua200433@126.com.
Hua
H
Yang
Department of Physiology, Second Military Medical University, No.800, Xiangyin Road, Shanghai, 200433, People's Republic of China. mmbb98@sohu.com.
Bei
B
Ma
D000818:Animals; D047629:Estrogen Receptor beta / Q000819:agonists*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D011422:Propionates
D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010080:Oxazoles; D058477:Receptors, Purinergic P2X3; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C478102:ERB 041
CFA; Estrogen receptor β; Inflammation; P2X3 receptor; TNBS