Effects of monoclonal antagonist antibodies on calcitonin gene-related peptide receptor function and trafficking

Raffi Manoukian,
Hong Sun,
Silke Miller,
Di Shi,
Brian Chan and
Cen XuEmail author

The Journal of Headache and PainOfficial Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"201920:44

https://doi.org/10.1186/s10194-019-0992-1

Received: 26 February 2019
Accepted: 4 April 2019
Published: 30 April 2019

Abstract

Background

Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are efficacious for the prevention of migraine headaches. The downstream molecular mechanisms following ligand-receptor blockade by which these antibodies prevent CGRP signaling through CGRP receptors have not been demonstrated.

Methods

Here we produced tool monoclonal functional antagonist antibodies against CGRP and its canonical receptor and developed a novel cellular model using fluorogen-activated protein technology that allows detection of CGRP receptor internalization by flow cytometry and, for an extended time course, visualization by confocal microscopy.

Results

Using this cell model we showed that these antagonist antibodies block both CGRP-induced cAMP signaling and CGRP receptor internalization. At least 10-fold higher concentrations of either antibody are necessary to block CGRP receptor internalization compared with cAMP accumulation in our cell model.