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Does bladder outlet obstruction alter the non-neuronal cholinergic system of the human urothelium?

机译:膀胱出口梗阻是否改变了人尿溶质的非神经元胆碱能系统?

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Alterations of the bladder sensory system are considered to contribute to detrusor overactivity (DO) when patients suffer from bladder outlet obstruction (BOO). The urothelium is one part of this sensory system and it harbors a non-neuronal cholinergic system (NNCS). We aimed to investigate if BOO causes alterations in the NNCS.Urothelial specimens were collected by endoscopy from six male controls and eight male patients suffering from BOO and DO. The samples were examined by immunofluorescence (IF) and real-time RT-PCR for high-affinity choline transporter-1 (CHT1), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), organic cation transporters OCT1-3, muscarinic receptor (mAChR) subtypes M1-M5 and nicotinic receptor (nAChR) subunits α7, α9 and α10.ChAT, VAChT and OCT2 are not present in the male urothelium. Real-time RT-PCR and IF detected all other investigated targets. Rank order of expression was M2?M3=M5>M4=M1 for mAChR subtypes and α7?α10>α9 for nAChR subunits. Statistical analysis of RT-PCR results did not detect significant differences between patients and controls. Only IF detected differences between both groups: α9-Immunolabeling was increased in all BOO/DO patients.BOO does not induce considerable alterations of the human urothelial NNCS on mRNA level. Expression of mAChRs, CHT1, OCT1 and OCT3 is not significantly affected by BOO. Thus, transport mechanisms for choline and acetylcholine (ACh) stay unaltered. BOO increases immunolabeling of α9-nAChR but whether this sole finding contributes to the onset of DO seems questionable. Comparing the present results with our previous work, the urothelial NNCS does not differ between men and women.
机译:当患者患有膀胱出口梗阻(BOO)时,认为膀胱感官系统的改变被认为有助于逼尿肌过度效力(DO)。尿路鞘是该感觉系统的一部分,它患有非神经元胆碱能系统(NNC)。我们的旨在调查BOO是否导致NNCS.UROPLELIAL样本的改变,通过内窥镜检查来自六个男性对照和八名男性患者患有嘘声的八个患者。通过免疫荧光(IF)和实时RT-PCR检查样品,用于高亲和力胆碱转运蛋白-1(CHT1),胆碱乙酰转移酶(聊天),囊泡乙酰胆碱转运蛋白(VACHT),有机阳离子转运蛋白,OCT1-3,肌肉蛋白受体(MACHR)亚型M1-M5和烟碱受体(NACHR)亚基α7,α9和α10.chat,Vacht和Oct2不存在于雄性尿浆中。实时RT-PCR,如果检测到所有其他调查的目标。表达的等级顺序是MACHR亚型的M2?M3 = M5> M4 = M1,NACHR亚基的α7α10>α9。 RT-PCR结果的统计分析未检测患者和对照之间的显着差异。仅当检测到两组之间的差异:α9-IMMUTOLING在所有嘘/患者中都有增加.BOO不会引起人类尿路上NNC对mRNA水平的相当大的改变。 MACHRS,CHT1,OCT1和OCT3的表达不会受到嘘声的显着影响。因此,胆碱和乙酰胆碱(ACH)保持不变的运输机制。嘘增加α9-NACHR的免疫标签,但这种唯一的发现是否有助于表现似乎是可疑的。将目前的结果与我们以前的工作相比,男女之间的尿路上皮NNC不会有所不同。

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