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Papers of the Week

Papers: 11 Apr 2020 - 17 Apr 2020

Pharmacology/Drug Development

2020 Apr 10

ACS Pharmacol Transl Sci



Distinct Patterns of Internalization of Different Calcitonin Gene-Related Peptide Receptors.


Gingell JJ, Rees TA, Hendrikse ER, Siow A, Rennison D, Scotter J, Harris PWR, Brimble MA, Walker CS, Hay DL
ACS Pharmacol Transl Sci. 2020 Apr 10; 3(2):296-304.
PMID: 32296769.


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 AMY 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 AMY receptor unexpectedly showing little internalization.