Suppression of Bladder Overactivity by Adenosine A2A Receptor Antagonist in a Rat Model of Parkinson Disease
Suppression of Bladder Overactivity by Adenosine A2A Receptor Antagonist in a Rat Model of Parkinson Disease
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DOI：
10.1016/j.juro.2011.12.062
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发表时间：
2012-05-01
影响因子：
6.6
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
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作者：
Kitta, Takeya;Chancellor, Michael B.;Yoshimura, Naoki
目的：膀胱过度活动症在帕金森病患者中非常普遍。腺苷是中枢神经系统中重要的神经递质，但腺苷受体如何调节排尿反射尚未完全阐明。因此，我们研究了腺苷A2 A受体拮抗剂对帕金森病大鼠模型排尿反射的影响。材料和方法：在6-羟基多巴胺诱导的帕金森病大鼠模型中，（Tocris Bioscience，Ellisville，密苏里州）注射，我们检测了腺苷A2 A受体拮抗剂ZM 241385，多巴胺D1受体激动剂SKF 38393和多巴胺D2受体激动剂喹吡罗对膀胱活动的影响。ZM 241385静脉给药可剂量依赖性地延长帕金森病大鼠和假手术大鼠的收缩间期，但其抑制作用不明显。在帕金森病组中更大。鞘内和侧脑室注射ZM 241385可增加各组的收缩间期。然而，在帕金森病大鼠中，侧脑室注射ZM 241385诱导的抑制作用大于假手术大鼠。静脉注射SKF 38393增加了帕金森病大鼠的收缩间期，随后注射ZM进一步增加了收缩间期。然而，SKF 38393没有增加ZM 241385应用后的收缩间期。此外，ZM 241385增加了intercontraction间隔，而不受预管理或后管理quinpirole，减少intercontraction interval.Conclusions：结果表明，腺苷A2 A受体介导的兴奋机制是增强在脊髓上的网站，诱导膀胱过度活动和A2 A受体抑制有效地抑制帕金森病大鼠膀胱过度活动。因此，腺苷A2 A受体拮抗剂可用于帕金森病病例中的膀胱功能障碍。
Purpose: Overactive bladder is highly prevalent among patients with Parkinson disease. Adenosine is an important neurotransmitter in the central nervous system but it is not fully clarified how adenosine receptors regulate the micturition reflex. Thus, we examined the effect of an adenosine A2A receptor antagonist on the micturition reflex in a rat model of Parkinson disease.Materials and Methods: In a rat model of Parkinson disease induced by 6-hydroxydopamine (Tocris Bioscience, Ellisville, Missouri) injection we examined the effects of the adenosine A2A receptor antagonist ZM241385, the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole on bladder activity.Results: Intravenous administration of ZM241385 increased the intercontraction interval in a dose dependent manner in rats with Parkinson disease and sham operated rats but the inhibitory effect was greater in the Parkinson disease group. Intrathecal and intracerebroventricular administration of ZM241385 increased the intercontraction interval in each group. However, in rats with Parkinson disease the inhibitory effects induced by intracerebroventricular administration of ZM241385 were greater than in sham operated rats. Intravenous administration of SKF38393 increased the intercontraction interval in rats with Parkinson disease and subsequent administration of ZM further increased the intercontraction interval. However, SKF38393 did not increase the intercontraction interval after ZM241385 application. Also, ZM241385 increased the intercontraction interval without being affected by pre-administration or post-administration of quinpirole, which decreased the intercontraction interval.Conclusions: Results indicate that the adenosine A2A receptor mediated excitatory mechanism is enhanced at a supraspinal site to induce bladder overactivity and A2A receptor inhibition effectively suppresses bladder overactivity in rats with Parkinson disease. Thus, adenosine A2A receptor antagonists could be useful for bladder dysfunction in Parkinson disease cases.