Fan Juan, Yu Li-Hua, Zhang Yanmin, Ni Xin, Ma Bei, Burnstock Geoffrey
Department of Physiology, Second Military Medical University, 800, Xiangyin Road, Shanghai, 200433, PR China.
Steroids. 2009 Nov;74(12):956-62. doi: 10.1016/j.steroids.2009.07.002. Epub 2009 Jul 21.
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.
P2X(3)和P2X(2/3)受体在外周组织和背根神经节（DRG）中表达，并参与外周疼痛。然而，不同卵巢激素水平下P2X受体介导伤害感受的机制尚未得到研究。在本研究中，24只雌性大鼠被随机分为假手术（sham）、卵巢切除（OVX）、雌激素处理和雌激素 - 孕激素处理的结肠炎组。在每组中，测试对结肠扩张的内脏运动反射（VMR），并采集DRG进行P2X(3)和P2X(2)受体mRNA的实时PCR分析。在患有结肠炎的OVX大鼠中，我们发现对结肠扩张的VMR和DRG中的P2X(3)受体mRNA均显著降低。雌激素替代可逆转这种降低。然而，雌激素和孕激素复合物并未逆转患有结肠炎的OVX大鼠的VMR或DRG中的P2X(3) mRNA水平。膜片钳记录显示，在结肠炎大鼠中，雌二醇在DRG神经元亚群中迅速将ATP诱发的持续电流和瞬态电流分别增强至对照的336±49%和122±12%，这被雌激素受体拮抗剂ICI 182,780阻断。而孕激素迅速将ATP诱导的瞬态电流抑制至对照的67±10%，并且对相同激动剂诱发的持续电流没有影响。这些结果表明，P2X(3)受体可能是结肠炎大鼠结肠功能改变的重要因素，其潜在机制与内源性雌激素调节密切相关。
