Expression and distribution of cholinergic receptors in the human urothelium
Expression and distribution of cholinergic receptors in the human urothelium
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DOI：
10.1016/j.lfs.2007.01.053
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发表时间：
2007-05-30
期刊：
影响因子：
6.1
通讯作者：
Lips, Katrin S.
中科院分区：
文献类型：
--
作者：
Bschleipfer, Thomas;Schukowski, Konstantin;Lips, Katrin S.
膀胱尿路上皮不仅提供扩散屏障，而且还起到传感器功能并释放被认为以旁分泌和自分泌方式起作用的信号分子，例如通过乙酰胆碱。其作用由两类受体赋予，即G蛋白偶联毒蕈碱受体（MR）和离子型烟碱受体（nAChR）。本研究采用RT-PCR和免疫组化方法分别检测了MR亚型（M1 R-M5 R）和nAChR α亚基7、9和10在人尿道上皮中的表达和分布。Real-time RT-PCR显示MR亚型表达的顺序为M2 R>> M3 R = M5 R> M4 R = M1 R。免疫组织化学显示差异分布模式，M1 R仅限于基底细胞，M2 R几乎仅见于伞细胞，而M3 R和M4 R均匀分布，M5 R从管腔到基底呈递减梯度。至于nAChR α-亚基，表达的等级顺序为α 7>> α 10> α 9，并且它们在整个尿路上皮中观察到，强度从管腔到基底梯度降低。总之，人尿路上皮携带多种胆碱能受体亚型，主要表达M2 R、M3 R和α 7-nAChR。它们的分布以及表达较少的亚型在尿路上皮中具有层特异性。鉴于不同的胆碱能受体亚型耦合的途径的多样性，我们建议，这种层特异性分布用于分层胆碱能调节人类尿路上皮功能。(c)2007年爱思唯尔公司All rights reserved.
The bladder urothelium not only provides a diffusion barrier but it also serves a sensor function and releases signalling molecules that are considered to act in a paracrine and autocrine fashion, e.g. by acetylcholine. Its actions are conferred by two classes of receptors, i.e. G-protein-coupled muscarinic receptors (MR) and ionotropic nicotinic receptors (nAChR). In this study we set out to determine the expression and distribution of all MR subtypes (M1R-M5R) and nAChR alpha-subunits 7, 9 and 10 in the human urothelium by means of RT-PCR and immunohistochemistry, respectively. Real-time RT-PCR revealed a rank order of MR subtype expression of M2R>>M3R=M5R>M4R=M1R. Immunohistochemistry demonstrated differential distribution patterns with M1R being restricted to basal cells, M2R nearly exclusively found in umbrella cells, whereas M3R and M4R were homogenously distributed and M5R was seen in a decreasing gradient from luminal to basal. As for nAChR alpha-subunits, rank order of expression is alpha 7>> alpha 10>alpha 9, and they were observed throughout the urothelium with a gradient decreasing from luminal to basal in intensity. In conclusion, the human urothelium carries multiple cholinergic receptor subtypes, with predominant expression of M2R, M3R and alpha 7-nAChR. Their distribution as well as that of the less expressed subtypes is layer-specific in the urothelium. In view of the multiplicity of pathways to which different cholinergic receptor subtypes are coupled, we propose that this layer-specific distribution serves to stratify cholinergic regulation of human urothelial function. (c) 2007 Elsevier Inc. All rights reserved.