Abstract：
Nicotinic acetylcholine receptors (nAChRs) belong to a superfamily of cys-loop receptors characterized by the assembly of five subunits into a multi-protein channel complex. Ligand binding to nAChRs activates rapid allosteric transitions of the receptor leading to channel opening and ion flux in neuronal and non-neuronal cell. Thus, while ionotropic properties of nAChRs are well recognized, less is known about ligand-mediated intracellular metabotropic signaling responses. Studies in neural and non-neural cells confirm ionotropic and metabotropic channel responses following ligand binding. In this review we summarize evidence on the existence of ionotropic and metabotropic signaling responses by homopentameric α7 nAChRs in various cell types. We explore how coordinated calcium entry through the ion channel and calcium release from nearby stores gives rise to signaling important for the modulation of cytoskeletal motility and cell growth. Amino acid residues for intracellular protein binding within the α7 nAChR support engagement in metabotropic responses including signaling through heterotrimeric G proteins in neural and immune cells. Understanding the dual properties of ionotropic and metabotropic nAChR responses is essential in advancing drug development for the treatment of various human disease.
摘要：
烟碱乙酰胆碱受体（nAChRs）属于cys-loop受体超家族，其特征在于将五个亚基组装成多蛋白通道复合物。与nAChRs结合的配体激活受体的快速变构转变,导致神经元和非神经元细胞中的通道开放和离子流。因此，虽然nAChRs的离子变性是公认的，对配体介导的细胞内代谢信号应答的了解较少。对神经细胞和非神经细胞的研究证实了配体结合后的离子型和代谢型通道反应。在这篇综述中，我们总结了同五聚体α7nAChRs在各种细胞类型中存在离子型和代谢型信号应答的证据。我们探索了通过离子通道的协调钙进入和附近商店的钙释放如何产生对细胞骨架运动和细胞生长的调节重要的信号。α7nAChR内用于细胞内蛋白结合的氨基酸残基支持参与代谢反应，包括通过神经和免疫细胞中的异源三聚体G蛋白进行信号传导。了解离子型和代谢型nAChR反应的双重特性对于推进用于治疗各种人类疾病的药物开发至关重要。
