Authentic role of ATP signaling in micturition reflex.
Authentic role of ATP signaling in micturition reflex.
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DOI：
10.1038/srep19585
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发表时间：
2016-01-22
影响因子：
4.6
通讯作者：
Shimada S
中科院分区：
文献类型：
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作者：
Takezawa K;Kondo M;Kiuchi H;Ueda N;Soda T;Fukuhara S;Takao T;Miyagawa Y;Tsujimura A;Matsumoto-Miyai K;Ishida Y;Negoro H;Ogawa O;Nonomura N;Shimada S
三磷酸腺苷(ATP)是一种调节细胞过程的信号分子。根据过去十年对膀胱功能的研究，膀胱ATP信号被认为在正常排尿反射中起着重要作用。在这项研究中，我们使用自动纸上尿染色法和视频尿动力学对嘌呤能受体缺陷小鼠的膀胱功能进行了详细的分析。出乎意料的是，在正常生理条件下，P2X2或P2X3受体的缺失并不影响膀胱功能，表明膀胱ATP信号对正常排尿反射并不是必需的。相反，我们发现脂多糖(LPS)诱导尿路上皮细胞释放出明显高水平的三磷酸腺苷。此外，P2X2−/−和P2X3−/−小鼠对脂多糖诱导的快速膀胱过度活动也有抑制作用。与以前的解释相反，我们目前的发现表明，在病理条件下，膀胱ATP信号在排尿反射中起着重要作用，特别是在膀胱功能障碍中。因此，膀胱ATP信号通路可能是治疗功能性膀胱疾病的一个很有前途的靶点。这项研究新定义了膀胱三磷酸腺苷信号在排尿反射中的真实作用。
Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2−/− and P2X3−/− mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex.