Human calcitonin gene-related peptide receptor (CGRP receptor)

The human calcitonin gene-related peptide (CGRP) receptor is a heteromeric G protein-coupled receptor (GPCR) essential for mediating the effects of CGRP, a potent neuropeptide vasodilator (1, 3). It is uniquely composed of two main subunits: the calcitonin receptor-like receptor (CALCRL) and the receptor activity-modifying protein 1 (RAMP1), which are required together for functional ligand binding and signaling (3, 8). The receptor is widely distributed in the nervous system, particularly within the trigeminal vascular system, where its activation triggers neurogenic inflammation and pain transmission associated with migraine (6, 14). Due to its central role in migraine pathophysiology, the CGRP receptor is a primary therapeutic target for both acute and preventive treatments (6, 13). Drugs targeting this receptor include small-molecule antagonists known as gepants and the monoclonal antibody erenumab, which block CGRP binding to alleviate or prevent headaches (6, 8). Beyond its role in pain, the receptor is involved in cardiovascular homeostasis and gastrointestinal motility, contributing to its clinical safety profile, which includes concerns such as constipation and blood pressure changes (1, 13).

Other names

CGRPRCGRP1 receptorCALCRL/RAMP1 complexCalcitonin receptor-like receptor/Receptor activity-modifying protein 1 complex

Competitive antagonism of the CGRP receptor and monoclonal antibody-mediated blockade of the receptor to prevent ligand binding and subsequent signaling (1, 6, 13).