Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists
Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists
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DOI：
10.1152/ajprenal.00436.2011
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发表时间：
2012-06-01
影响因子：
4.2
通讯作者：
Kanai, A. J.
中科院分区：
文献类型：
--
作者：
Fry, C. H.;Young, J. S.;Kanai, A. J.
Fry CH，Young JS，Jabr RI，McCarthy C，Ikeda Y，Kanai AJ。过度活跃膀胱中自发活动的调节：P2Y激动剂的作用。Am J Physiol Renal Physiol 302：F1447-F1454,2012。首次发表于2012年2月22日；DOI：10.1152/ajprenal.00436.2011。-脊髓横断术(SCT)导致孤立膀胱的自发收缩活动增加，这使具有类似中枢神经系统损伤的患者的膀胱过度活动综合症联想到。在SCT膀胱中，尿路上皮和逼尿肌层之间的尿路上皮下间隙的间质细胞数量增加，这些细胞对嘌呤和嘧啶类物质如ATP、ADP和UTP产生兴奋反应。我们调查了一种假设，即这些药物是自发活动增加的基础。大鼠接受下胸段脊髓横断，其膀胱片或膀胱条，除特殊情况外，具有完整的粘膜，用于实验。记录等长张力，用光电二极管阵列荧光成像记录钙离子传播波和膜电位(E-m)波。SCT膀胱与规律性自发收缩有关(2.9+/-0.4次/分钟)；ADP、UTP和UDP增加幅度，但不增加频率。对于这种膀胱的条带，P2Y(6)选择性激动剂(PSB0474)也起到了类似的作用。膀胱片的荧光成像显示，ADP或UTP增加了局限于膀胱壁黏膜完整区域的钙/E-m波的传导速度。当采用膀胱横切面时，Ca~(2+)/E-m波起源于膀胱上皮下间隙，并传播到逼尿肌和尿路上皮。波传播分析表明，上皮下间隙表现出电联合的特性。这些实验与这样的假设是一致的，即P2Y受体激动剂通过增强上皮下间隙细胞合体的功能活动来增加自发收缩活动。
Fry CH, Young JS, Jabr RI, McCarthy C, Ikeda Y, Kanai AJ. Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists. Am J Physiol Renal Physiol 302: F1447-F1454, 2012. First published February 22, 2012; doi:10.1152/ajprenal.00436.2011.-Spinal cord transection (SCT) leads to an increase in spontaneous contractile activity in the isolated bladder that is reminiscent of an overactive bladder syndrome in patients with similar damage to the central nervous system. An increase in interstitial cell number in the suburothelial space between the urothelium and detrusor smooth muscle layer occurs in SCT bladders, and these cells elicit excitatory responses to purines and pyrimidines such as ATP, ADP, and UTP. We have investigated the hypothesis that these agents underlie the increase in spontaneous activity. Rats underwent lower thoracic spinal cord transection, and their bladder sheets or strips, with intact mucosa except where specified, were used for experiments. Isometric tension was recorded and propagating Ca2+ and membrane potential (E-m) waves were recorded by fluorescence imaging using photodiode arrays. SCT bladders were associated with regular spontaneous contractions (2.9 +/- 0.4/min); ADP, UTP, and UDP augmented the amplitude but not their frequency. With strips from such bladders, a P2Y(6)-selective agonist (PSB0474) exerted similar effects. Fluorescence imaging of bladder sheets showed that ADP or UTP increased the conduction velocity of Ca2+/E-m waves that were confined to regions of the bladder wall with an intact mucosa. When transverse bladder sections were used, Ca2+/E-m waves originated in the suburothelial space and propagated to the detrusor and urothelium. Analysis of wave propagation showed that the suburothelial space exhibited properties of an electrical syncitium. These experiments are consistent with the hypothesis that P2Y-receptor agonists increase spontaneous contractile activity by augmenting functional activity of the cellular syncitium in the suburothelial space.