Yiangou Y, Facer P, Ford A, Brady C, Wiseman O, Fowler C J, Anand P
Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London.
BJU Int. 2001 Jun;87(9):774-9. doi: 10.1046/j.1464-410x.2001.02190.x.
To determine the presence, distribution and molecular forms of the vanilloid receptor VR1, and confirm the presence and distribution of the ATP-gated ion channel P2X3 in the human urinary bladder. Materials and methods Normal urinary bladder tissues were obtained at postmortem from four subjects. Eight urinary bladder biopsies were also taken from patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin. The specimens were studied using affinity-purified specific antibodies to VR1 and P2X3 by Western blotting and immunocytochemistry, and compared with immunostaining using antibodies to the pan-neuronal marker PGP 9.5 and Schwann cell marker S-100.
VR1- and P2X3-immunoreactive fine nerve fibres were scattered throughout the suburothelium of the normal bladder and cystoscopic biopsies, and traversed the muscle layer. They had a similar distribution to PGP 9.5-immunoreactive fibres, but there were fewer, suggesting localization in subsets of axons. Western blot studies showed an expected 100-kDa VR1 protein and a P2X3-immunoreactive 66-kDa protein. Conclusion VR1 and P2X3 are present in the human urinary bladder and may contribute to distinct pathophysiological states of bladder overactivity, in accord with their differential expression in sensory neurones. Intravesical vanilloids act via VR1 and are effective in the treatment of detrusor hyper-reflexia. P2X3 may represent a selective therapeutic target for other causes of overactive bladder.
确定香草酸受体VR1的存在、分布及分子形式，并证实三磷酸腺苷门控离子通道P2X3在人膀胱中的存在及分布。材料与方法 从4名受试者尸检时获取正常膀胱组织。还从膀胱内注射树脂毒素治疗的逼尿肌反射亢进患者身上取了8份膀胱活检组织。通过蛋白质免疫印迹法和免疫细胞化学，使用针对VR1和P2X3的亲和纯化特异性抗体对标本进行研究，并与使用针对泛神经元标志物PGP 9.5和雪旺细胞标志物S - 100的抗体进行免疫染色的结果进行比较。
VR1和P2X3免疫反应性细神经纤维散布于正常膀胱和膀胱镜活检组织的尿路上皮下层，并穿过肌肉层。它们的分布与PGP 9.5免疫反应性纤维相似，但数量较少，提示定位于轴突亚群。蛋白质免疫印迹研究显示预期的100 kDa VR1蛋白和P2X3免疫反应性66 kDa蛋白。结论 VR1和P2X3存在于人膀胱中，可能与膀胱过度活动的不同病理生理状态有关，这与其在感觉神经元中的差异表达一致。膀胱内注射香草酸类药物通过VR1起作用，对治疗逼尿肌反射亢进有效。P2X3可能是膀胱过度活动其他病因的选择性治疗靶点。
