PDF(Pubmed)
Abstract：
Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.
摘要：
乙酰胆碱激活的受体大致分为两个主要的结构上不同的类别:配体门控离子通道烟碱型和G蛋白偶联的毒蕈碱型受体。每一类包括几种结构相关的受体亚型,具有不同的组织表达模式和受体后信号转导机制。烟碱和毒蕈碱胆碱能受体的激活与胃肠道肿瘤的诱导和进展有关。在这里，在简要回顾了乙酰胆碱激活受体的分类以及烟碱和毒蕈碱胆碱能信号在正常消化功能中的作用后，我们考虑了胃肠微环境中神经元和非神经元细胞合成和释放乙酰胆碱的机制，以及目前准确测量血清和组织乙酰胆碱水平的方法和挑战。然后，我们严格评估了组成型和配体诱导的乙酰胆碱激活受体激活在促进胃肠道肿瘤形成中起作用的证据.我们主要关注胃腺癌，胰腺,和结肠，因为这些癌症在世界范围内特别常见，当被诊断为晚期时，与非常高的发病率和死亡率有关。在整个全面审查中，我们专注于寻找新的方法来利用这些观察结果进行预后和治疗.
