Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice
Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice
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DOI：
10.1152/ajprenal.00054.2008
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
Thorneloe, Kevin S.
中科院分区：
文献类型：
--
作者：
McCafferty, Gerald P.;Misajet, Blake A.;Thorneloe, Kevin S.
非甾体类抗炎环氧合酶抑制剂，其功能是减少前列腺素E-2（PGE（2））的生产已被广泛报道为膀胱过度活动模型的有效药物。因此，我们通过对EP 3受体敲除（KO）小鼠进行清醒、自由活动的膀胱测压，研究了PGE（2）受体EP 3在膀胱功能中的潜在作用。与野生型（WT）小鼠相比，EP 3 KO小鼠在对照条件下表现出膀胱容量增强（与WT的185%相似），这是基于更大的排尿和输注膀胱体积。将EP 3受体激动剂GR 63799 X输注到WT小鼠的膀胱中降低了膀胱容量。这在EP 3 KO小鼠中无效，该小鼠证明了GR 63799 X的膀胱容量的时间依赖性增加，这与在两种基因型中用媒介物观察到的效果相似。此外，将PGE（2）输注到WT小鼠中可诱导膀胱过度活动，这种作用在EP 3 KO小鼠中显著减弱。本文报道的数据提供了支持EP 3受体在正常膀胱功能中的功能作用的第一个证据，并暗示EP 3在增强PGE 2产生的病理条件下作为膀胱过度活动的贡献者，如先前在膀胱过度活动症患者中报道的那样。
Nonsteroidal anti-inflammatory cyclooxygenase inhibitors that function to reduce prostaglandin E-2 (PGE(2)) production have been widely reported as effective agents in models of urinary bladder overactivity. We therefore investigated a potential role for the PGE(2) receptor, EP3, in urinary bladder function by performing conscious, freely moving cystometry on EP3 receptor knockout (KO) mice. EP3 KO mice demonstrated an enhanced bladder capacity compared with wild-type (WT) mice (similar to 185% of WT) under control conditions, based on larger voided and infused bladder volumes. Infusion of the EP3 receptor agonist GR63799X into the bladder of WT mice reduced the bladder capacity. This was ineffective in EP3 KO mice that demonstrated a time-dependent increase in bladder capacity with GR63799X, an effect similar to that observed with vehicle in both genotypes. In addition, infusion of PGE(2) into WT mice induced bladder overactivity, an effect that was significantly blunted in the EP3 KO mice. The data reported here provide the first evidence supporting a functional role for EP3 receptors in normal urinary bladder function and implicate EP3 as a contributor to bladder overactivity during pathological conditions of enhanced PGE2 production, as reported previously in overactive bladder patients.