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Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium.

机译:食管上皮中非神经元乙酰胆碱合成和释放机制的改变。

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A non-neuronal cholinergic system has been described in epithelial cells including that of the urinary bladder (urothelium) and the upper gastrointestinal tract (esophagus). Epithelial dysfunction has been implicated in the pathophysiology of persistent pain conditions such as painful bladder syndrome as well as functional heartburn. For example, alterations in the ability to synthesize and release acetylcholine may contribute to changes in epithelial sensory and barrier function associated with a number of functional genitourinary and intestinal disorders.We examined using immunoblot, acetylcholine (ACh)-synthesis and release components in cat esophageal mucosa and whether elements of these components are altered in a naturally occurring model of chronic idiopathic cystitis termed feline interstitial cystitis (FIC).We identified proteins involved in ACh synthesis and release (high affinity choline transporter, CHT1; ACh synthesizing enzyme choline acetyltransferase ChAT and carnitine acetyltransferase CarAT; vesicular ACh transporter VAChT and the organic cation transporter isoforms 1-3 or OCT-1-3) in cat esophageal mucosa. Significant alterations in CHT, ChAT, VAChT and OCT-1 were detected in the esophageal mucosa from FIC cats. Changes in the vesicular nucleotide transporter (VNUT) and the junctional protein pan-cadherin were also noted.Taken together, these findings suggest that changes in the non-neuronal cholinergic system may contribute to alterations in cell-cell contacts and possibly communication with underlying cells that may contribute to changes in sensory function and visceral hyperalgesia in functional esophageal pain.
机译:已经在包括膀胱(尿道上皮)和上消化道(食道)的上皮细胞中描述了非神经胆碱能系统。上皮功能障碍与持续性疼痛状况的病理生理有关,例如疼痛性膀胱综合症以及功能性烧心。例如,乙酰胆碱的合成和释放能力的改变可能会导致与许多泌尿生殖系统和肠道功能紊乱有关的上皮感觉和屏障功能的改变。我们使用免疫印迹,乙酰胆碱(ACh)合成和释放在食管猫中进行了研究在称为猫间质性膀胱炎(FIC)的慢性特发性膀胱炎的自然发生模型中,我们发现了参与ACh合成和释放的蛋白质(高亲和力胆碱转运蛋白CHT1; ACh合成酶胆碱乙酰基转移酶ChAT和肉碱乙酰基转移酶CarAT;猫食管粘膜中的囊泡ACh转运蛋白VAChT和有机阳离子转运蛋白同工型1-3或OCT-1-3)。在FIC猫的食管粘膜中检测到CHT,ChAT,VAChT和OCT-1的显着改变。囊泡核苷酸转运蛋白(VNUT)和连接蛋白pan-cadherin的变化也被注意到,总的来说,这些发现表明非神经元胆碱能系统的变化可能有助于细胞间接触的改变,并可能与基础细胞沟通可能会导致功能性食管疼痛的感觉功能和内脏痛觉过敏发生变化。

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