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

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. CONCLUSION:These data reinforce our understanding of how monoclonal functional antagonist antibodies interfere with CGRP signaling.

SUBMITTER: Manoukian R 

PROVIDER: S-EPMC6734291 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature