Non-neuronal acetylcholine and urinary bladder urothelium
Non-neuronal acetylcholine and urinary bladder urothelium
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DOI：
10.1016/j.lfs.2007.02.010
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发表时间：
2007-05-30
期刊：
影响因子：
6.1
通讯作者：
Birder, Lori A.
中科院分区：
文献类型：
--
作者：
Hanna-Mitchell, Ann T.;Beckel, Jonathan M.;Birder, Lori A.
乙酰胆碱(ACh)的非神经性释放被认为在膀胱功能中起作用。这些研究探讨了从大鼠膀胱分离培养的尿路上皮细胞中非神经性胆碱能系统的表达和功能。我们的研究结果表明，尿路上皮细胞表达高亲和力胆碱转运体(CHT1)和乙酰胆碱合成酶、胆碱乙酰转移酶(ChAT)和肉碱乙酰转移酶(CARAT)。与神经元不同，尿路上皮细胞不表达囊泡型乙酰胆碱转运体(VAChT)，但表达Oct3，这是多特异性有机阳离子转运体(OCT)的一种亚型，被认为参与了非神经细胞释放乙酰胆碱的过程。培养的尿路上皮细胞暴露于H-3-胆碱后，检测到细胞内的放射性，并通过机械刺激(将细胞暴露于50%低渗Krebs中)或100 mU三磷酸腺苷化学刺激嘌呤能受体而引起放射性释放增加。目前的实验没有确定诱发的放射性释放(在本文中称为H-3-ACh释放)是由于乙酰胆碱还是胆碱的释放。单独应用乙酰胆碱不能引起H-3-ACh的释放，但非选择性M受体拮抗剂阿托品可促进H-3-ACh的释放，提示尿路上皮细胞释放的乙酰胆碱可能通过作用于M受体而抑制自身在尿路上皮的释放而参与负反馈机制。Brefeldin是一种破坏囊泡胞吐的药物，但不能阻止低张诱发的H-3-ACh的释放。这些观察表明，尿路上皮细胞释放乙酰胆碱的机制与神经递质释放所依赖的囊泡储存和胞吐作用不同。(C)2007 Elsevier Inc.保留所有紧身衣。
Non-neuronal release of acetylcholine (ACh) has been proposed to play a role in urinary bladder function. These studies investigated the expression and function of the non-neuronal cholinergic system in cultured urothelial cells isolated from the rat urinary bladder. Our findings have revealed that urothelial cells express the high-affinity choline transporter (CHT1) and acetylcholine-synthesizing enzymes, choline acetyltransferase (ChAT) and carnitine acetyltransferase (CarAT). In contrast to neurons, urothelial cells do not express the vesicular acetylcholine transporter (VAChT) but do express OCT3, a subtype of polyspecific organic cation transporter (OCT) that is thought to be involved in the release of acetylcholine from non-neuronal cells. Following exposure of cultured urothelial cells to H-3-choline, radioactivity was detected in the cells and increased release of radioactivity into the eternal media was evoked by mechanical stimulation (exposure of the cells to 50% hypotonic Krebs) or chemical stimulation of purinergic receptors by 100 mu M ATP. The present experiments did not establish if the evoked release of radioactivity (termed H-3-ACh release in this paper) was due to release of acetylcholine or choline. H-3-ACh release was not evoked by application of acetylcholine alone, however pretreatment with the non-selective muscarinic receptor antagonist atropine prior to application of acetylcholine facilitated H-3-ACh release, suggesting that the acetylcholine released from urothelial cells may participate in a negative feedback mechanism by acting on muscarinic receptors to inhibit its own release in the urothelium. Brefeldin, an agent which disrupts vesicular exocytosis, did not block hypotonic-evoked H-3-ACh release. These observations indicate that acetylcholine release from urothelial cells is mediated by different mechanisms than those such as vesicular storage and exocytosis that underlie the release of neurotransmitters from nerves. (c) 2007 Elsevier Inc. All tights reserved.