Distinct Patterns of Internalization of Different Calcitonin Gene-Related Peptide Receptors.,ACS Pharmacology & Translational Science

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Distinct Patterns of Internalization of Different Calcitonin Gene-Related Peptide Receptors.
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-02-26 , DOI: 10.1021/acsptsci.9b00089
Joseph J Gingell _{1,

2} , Tayla A Rees _{1,

2} , Erica R Hendrikse _{1,

2} , Andrew Siow _{1,

3} , David Rennison _{2,

3} , John Scotter ₄ , Paul W R Harris _{1,

2,

3} , Margaret A Brimble _{1,

2,

3} , Christopher S Walker _{1,

2} , Debbie L Hay _{1,

2,

5}

Affiliation

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is involved in the transmission of pain. Drugs targeting CGRP or a CGRP receptor are efficacious in the treatment of migraine. The canonical CGRP receptor is a complex of a G protein-coupled receptor, the calcitonin-like receptor (CLR), with an accessory protein, receptor activity-modifying protein 1 (RAMP1). A second receptor, the AMY1 receptor, a complex of the calcitonin receptor with RAMP1, is a dual high-affinity receptor for CGRP and amylin. Receptor regulatory processes, such as internalization, are crucial for controlling peptide and drug responsiveness. Given the importance of CGRP receptor activity in migraine we compared the internalization profiles of both receptors for CGRP using novel fluorescent probes and a combination of live cell imaging, fixed cell imaging, and ELISA. This revealed stark differences in the regulation of each receptor with the AMY1 receptor unexpectedly showing little internalization.

中文翻译：

不同的降钙素基因相关肽受体的内在化的独特模式。

降钙素基因相关肽（CGRP）是一种神经肽，与疼痛的传递有关。靶向CGRP或CGRP受体的药物可有效治疗偏头痛。规范的CGRP受体是G蛋白偶联受体降钙素样受体（CLR）与辅助蛋白受体活性修饰蛋白1（RAMP1）的复合体。第二种受体AMY1受体是降钙素受体与RAMP1的复合物，是CGRP和胰岛淀粉样多肽的双重高亲和力受体。受体调节过程（例如内在化）对于控制肽和药物反应性至关重要。考虑到CGRP受体活性在偏头痛中的重要性，我们使用新型荧光探针以及活细胞成像，固定细胞成像和ELISA的组合比较了CGRP两种受体的内在分布。

更新日期：2020-02-26

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