Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells
Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells
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DOI：
10.1152/ajprenal.00098.2005
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Birder, LA
中科院分区：
文献类型：
--
作者：
Beckel, JM;Kanai, A;Birder, LA
大鼠膀胱上皮细胞功能性尼古丁乙酰胆碱受体的表达。美国肾脏生理学杂志290：F103-F110，2006年。首次发表于2005年9月6日; doi：10.1152/ajprenal.00098.2005。尽管中枢和外周神经系统中的烟碱乙酰胆碱受体在控制膀胱功能中起着重要作用，但关于烟碱受体在膀胱上皮或尿道上皮中的表达或功能知之甚少。尼古丁受体已被描述在上胃肠道、呼吸道和皮肤的上皮细胞中。因此，本研究探讨了烟碱受体的表达和功能的尿路刺激，以及刺激的排尿反射的烟碱受体的影响。使用RT-PCR在大鼠尿路上皮细胞中鉴定α（3）、α（5）、α（7）、β（3）和β（4）烟碱亚基的mRNA。蛋白质印迹法也证实了尿路上皮表达的α（3）-和α（7）-亚基。应用尼古丁（50 nM）培养的大鼠尿路上皮细胞引起细胞内Ca（2+）浓度的增加，表明至少有一些亚基形成功能通道。这些作用被阻断的烟碱拮抗剂六甲双铵的应用。在体内膀胱cystometrograms在麻醉大鼠，膀胱内给药尼古丁，胆碱，或拮抗剂methylycaconitine柠檬酸盐和六甲铵引起排尿参数的变化。膀胱内尼古丁（50 nM，1 μ M）增加了收缩间期。膀胱内胆碱（1-100 μ M）也同样影响膀胱反射，表明α（7）烟碱受体介导了这种作用。膀胱内施用六甲双铵（1-100 μ M）增强尼古丁诱导的膀胱反射变化。特异性α（7）受体拮抗剂Methyllycaconitine citrate可预防尼古丁、胆碱和六甲铵诱导的膀胱抑制。这些结果是第一个迹象表明，刺激膀胱中的非神经元烟碱受体可以影响排尿。
Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells. Am J Physiol Renal Physiol 290: F103-F110, 2006. First published September 6, 2005; doi:10.1152/ajprenal.00098.2005.- Although nicotinic acetylcholine receptors in both the central and peripheral nervous systems play a prominent role in the control of urinary bladder function, little is known regarding expression or function of nicotinic receptors in the bladder epithelium, or urothelium. Nicotinic receptors have been described in epithelial cells lining the upper gastrointestinal tract, respiratory tract, and the skin. Thus the present study examined the expression and functionality of nicotinic receptors in the urothelium, as well as the effects of stimulation of nicotinic receptors on the micturition reflex. mRNA for the alpha(3), alpha(5), alpha(7), beta(3), and beta(4) nicotinic subunits was identified in rat urothelial cells using RT-PCR. Western blotting also confirmed urothelial expression of the alpha(3)- and alpha(7)-subunits. Application of nicotine (50 nM) to cultured rat urothelial cells elicited an increase in intracellular Ca(2+) concentration, indicating that at least some of the subunits form functional channels. These effects were blocked by the application of the nicotinic antagonist hexamethonium. During in vivo bladder cystometrograms in urethane-anesthetized rats, intravesical administration of nicotine, choline, or the antagonists methyllycaconitine citrate and hexamethonium elicited changes in voiding parameters. Intravesical nicotine (50 nM, 1 mu M) increased the intercontraction interval. Intravesical choline (1-100 mu M) also affected bladder reflexes similarly, suggesting that alpha(7) nicotinic receptors mediate this effect. Intravesical administration of hexamethonium (1-100 mu M) potentiated the nicotine-induced changes in bladder reflexes. Methyllycaconitine citrate, a specific alpha(7)-receptor antagonist, prevented nicotine-, choline-, and hexamethonium-induced bladder inhibition. These results are the first indication that stimulation of nonneuronal nicotinic receptors in the bladder can affect micturition.