HEART ATRIAL MUSCARINIC RECEPTOR

心房毒蕈碱受体

• 批准号: 2215676
• 负责人: Michael Schimerlik
• 金额: $ 27.45万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-12-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215676
• 关键词: CHO cells; G protein; atrium; biological signal transduction; circular dichroism; conformation; fluorescent dye /probe; heart pharmacology; ligands; muscarinic receptor; protein purification; protein reconstitution; protein structure function; receptor binding; receptor coupling; recombinant proteins; site directed mutagenesis; stop flow technique; swine; tissue /cell culture; ultraviolet spectrometry

Muscarinic cholinergic receptors in the atria mediate the regulation of the heart by the parasympathetic nervous systems. In order to obtain detailed information regarding the molecular mechanism of atrial muscarinic receptor signal transduction two approaches are proposed. The first is to use site- directed mutagenesis to explore the roles of specific amino acids in ligand binding, thermal stability and coupling to either endogenous Chinese Hamster ovary (CHO) cell G proteins or to atrial Gi reconstituted into CHO cell membranes. The second approach is to use biophysical methods such as circular dichroism and transient kinetics to examine changes in secondary structure that occur when ligands bind to the purified recombinant protein or to detect and analyze protein conformational changes that occur in the membrane-bound or purified preparations. Interaction of defined Gialpha1,2,3, with atrial Gibetagamma and muscarinic receptors, by resolving purified atrial gi into gil and Gi3 or by purifying Gi1,2,3 from brain and erythrocytes. The detailed knowledge of muscarinic mechanisms in the heart may be useful in the rational design of drugs for use in treating cardiac arrhymias as tachycardia.

心房中的M胆碱能受体介导对 心脏受到副交感神经系统的影响。为了获得详细的信息 心房M受体分子机制的研究进展 提出了两种信号转导途径。第一个是使用网站- 定向诱变探索特定氨基酸在配体中的作用 与内源性中国人的结合、热稳定性和偶联 仓鼠卵巢(CHO)细胞G蛋白或房性GI重组为CHO 细胞膜。第二种方法是使用生物物理方法，如 用圆二色谱和瞬变动力学研究次生元素的变化 当配体与纯化的重组蛋白结合时出现的结构 或检测和分析蛋白质构象的变化 膜结合制剂或纯化制剂。已定义的交互 Gialpha1，2，3，具有心房Gibetagamma和M受体，通过 纯化的心房Gi分离为GIL和GI3或从GI1，2，3提纯 大脑和红细胞。对毒鼠强作用机制的详细了解 心脏可能有助于合理设计用于治疗的药物。 心律失常如心动过速。