Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats.
Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats.
复制标题
DOI：
10.1111/j.1464-410x.2010.09260.x
复制
发表时间：
2010-12
影响因子：
4.5
通讯作者：
Chancellor MB
中科院分区：
文献类型：
--
作者：
Chuang YC;Yoshimura N;Huang CC;Wu M;Tyagi P;Chancellor MB
目的：探讨前列腺素E2(PGE2)膀胱内注射前列腺素E2(PGE2)通过激活EP受体和敏化传入神经诱导大鼠膀胱过度活动(OAB)过程中E系列前列腺素(EP1-EP4)受体4种亚型的表达及EP4受体拮抗剂(AH23848)对尿流动力学的影响。实验组和对照组大鼠分别腹腔注射CYP(200 mg/kg)或生理盐水。在乌拉坦麻醉下，分别于注射CYP或生理盐水后48h行连续膀胱测压(CMG)。AH23848按0.01 mg/kg和0.1 mg/kg的剂量静脉注射。然后取膀胱进行组织学检查。在没有进行CMG研究的情况下，采集一些膀胱用于Western blotting分析EP受体的表达。测量CMG变量(基线压力、收缩间期[ICI]、压力阈值[PT]、收缩幅度)和组织学变化。CYP诱导的EP4受体表达上调(100%)，并伴有逼尿肌过度活动(ICI降低70.5%，PT升高67.7%)。但CYP可下调EP1受体的表达(减少51.9%)，但对EP2和EP3受体无明显影响。AH23848可显著延长CYP组大鼠的ICI，但对其他尿动力学指标及对照组大鼠无明显影响。EP受体的调节在CYP诱导的OAB中起一定作用。EP4受体拮抗剂可能成为治疗OAB的新靶点。
To investigate the expression of four subtypes of E-series prostaglandin (EP1–EP4) receptors and the urodynamic effects of an EP4 receptor antagonist (AH23848) in cyclophosphamide (CYP)-induced overactive bladder (OAB) in rats, as intravesical prostaglandin E2 (PGE2) induces OAB via activation of EP receptors and sensitization of afferent nerves. Experimental and control rats were injected with CYP (200 mg/kg, intraperitoneally) or saline, respectively. Continuous cystometrograms (CMGs) were performed 48 h after CYP or saline injection under urethane anaesthesia. AH23848 was given intravenously at doses of 0.01 and 0.1 mg/kg. The bladder was then harvested for histology. Some bladders were harvested for analysis of EP receptors expression by Western blotting without a CMG study. CMG variables (baseline pressure; intercontraction interval [ICI], pressure threshold [PT], contraction amplitude) and histological changes were measured. CYP-induced up-regulation of EP4 receptor (100% increase) accompanied by detrusor overactivity (ICI 70.5% decrease; PT, 67.7% increase). However, CYP down-regulated EP1 receptor expression (51.9% decrease), but had no significant effects on the EP2 and EP3 receptors. AH23848 significantly extended the ICI in CYP-treated rats but it had no effects on other urodynamic variables or in control rats. Modulation of EP receptors plays a role in CYP-induced OAB. Antagonists to the EP4 receptor may be a new target for treatment of patients with OAB.