高含量筛选监测G蛋白偶联受体内化。

R Heilker
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引用次数: 8

摘要

G蛋白偶联受体(gpcr)在神经传递、呼吸、心血管作用、疼痛等领域发挥着广泛的生理功能。因此,它们被认为是制药市场上最成功的一组治疗靶点,而寻找以特定和选择性的方式干扰GPCR功能的化合物是制药行业的主要焦点。高含量筛选(HCS)是荧光显微成像和自动图像分析的结合,已成为细胞疾病建模系统中研究测试复合效应的常用工具。通过HCS分析测试化合物对gpcr的功能影响的一种方法依赖于广泛观察到的脱敏现象。大多数GPCR的激动剂刺激导致其细胞内磷酸化和随后的内化,导致受体信号传导的终止和GPCR从进一步的细胞外刺激中隔离。作为其他功能性GPCR药物发现分析的补充,GPCR内化分析能够对测试化合物进行脱敏的药理学分析。
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High content screening to monitor G protein-coupled receptor internalisation.

G protein-coupled receptors (GPCRs) fulfil a broad diversity of physiological functions in areas such as neurotransmission, respiration, cardiovascular action, pain and more. Consequently, they are considered as the most successful group of therapeutic targets on the pharmaceutical market, and the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry. High Content Screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently employed tool to study test compound effects in cellular disease modelling systems. One way to functionally analyse the effect of test compounds on GPCRs by HCS relies on the broadly observed phenomenon of desensitisation. Agonist stimulation of most GPCRs leads to their intracellular phosphorylation and subsequent internalisation, resulting in the termination of receptor signalling and the seclusion of the GPCR from further extracellular stimulation. Complementary to other functional GPCR drug discovery assays, GPCR internalisation assays enable a desensitisation-focussed pharmacological analysis of test compounds.

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