Estrogen altered visceromotor reflex and P2X(3) mRNA expression in a rat model of colitis.
P2X(3) and P2X(2/3) receptors are expressed in peripheral tissues and dorsal root ganglia (DRG) and participate in peripheral pain. However, the mechanisms underlying P2X receptor-mediated nociception at different ovarial hormone levels has not been examined. In this study, 24 female rats were randomly divided into sham-operated (sham), ovariectomized (OVX), estrogen-treated, and estrogen-progesterone-treated groups with colitis. In each group, the visceromotor reflex (VMR) to colorectal distension was tested and the DRG were harvested for a real-time PCR analysis of P2X(3) and P2X(2) receptor mRNA. In OVX rats with colitis we found that the VMR to colorectal distension and P2X(3) receptor mRNA in DRG were both significantly decreased. Estrogen replacement reversed the decrease. However, neither the VMR nor the P2X(3) mRNA level in DRG from OVX colitis rats was reversed by the complex of estrogen and progesterone. Patch-clamp recording showed that in colitis rats, estradiol rapidly potentiated the sustained and transient currents evoked by ATP to 336+/-49% and 122+/-12% of controls, respectively, in a subpopulation of DRG neurons, which were blocked by ICI 182, 780, an antagonist of the estrogen receptor. Whereas progesterone rapidly inhibited the transient currents induced by ATP to 67+/-10% of control and had no effect on the sustained currents evoked by the same agonist. These results indicate that P2X(3) receptors are likely to be an important contributor to the altered colonic functions in colitis rats, where the underlying mechanisms are closely related to endogenous estrogen modulation.
Fan
Juan
J
Department of Physiology, Second Military Medical University, 800, Xiangyin Road, Shanghai, 200433, PR China.
Yu
Li-Hua
LH
Zhang
Yanmin
Y
Ni
Xin
X
Ma
Bei
B
Burnstock
Geoffrey
G
D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004553:Electric Conductivity; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D012018:Reflex / Q000187:drug effects*; D014781:Viscera / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology
D004967:Estrogens; C546401:P2RX2 protein, human; C546407:P2RX3 protein, human; C546403:P2rx2 protein, rat; C546410:P2rx3 protein, rat; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D011374:Progesterone