CGRP

CGRP Full Name

Calcitonin Gene Related Peptide

CGRP Introduction

Calcitonin gene-related peptide (CGRP) is a highly potent, 37-amino acid neuropeptide widely distributed throughout the central and peripheral nervous systems. Produced by the alternative splicing of the calcitonin gene, it exists in two primary isoforms: alpha-CGRP, predominantly found in sensory neurons, and beta-CGRP, mainly localized in the enteric nervous system. At the cellular level, CGRP exerts its biological effects by binding to a unique heterodimeric receptor complex composed of the calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1).

Figure 1. The cryo-EM structure of CGRP–CLR–RAMP1–G_s reveals molecular details of the RAMP-receptor interface. (Source: Liang YL, et al. 2018)

Functionally, CGRP is recognized as one of the most powerful endogenous vasodilators known in human physiology. Beyond its robust vasoactive properties, it plays a critical role as a key neurotransmitter in nociception (pain signaling) and acts as a major mediator of neurogenic inflammation by facilitating the release of inflammatory mediators and increasing vascular permeability. Because of its central role in vascular dynamics and pain transmission, the dysregulation of CGRP signaling is deeply implicated in several pathological conditions, most notably migraine headaches.

During a migraine attack, circulating levels of CGRP are significantly elevated, particularly within the trigeminovascular system. This leads to intense cranial vasodilation, neurogenic inflammation, and the subsequent sensitization of peripheral and central pain pathways. The overwhelming clinical evidence identifying CGRP as a fundamental driver of migraine pathophysiology has revolutionized the treatment landscape for this debilitating neurological disorder. In contemporary neuropharmacology, the CGRP pathway has become a premier therapeutic target. This has led to the successful development and clinical approval of novel classes of highly specific therapies, including small-molecule CGRP receptor antagonists (gepants) and monoclonal antibodies targeting either the CGRP ligand itself or its receptor, marking a major breakthrough in modern biotechnology and neurology.

Alternate Names for CGRP

Calcitonin/calcitonin related polypeptide alpha; Alpha type CGRP; Beta type CGRP; yCALC 1; CALC A; CALC1; CALC2; CALCA; CALCB; Calcitonin 1

• Immunohistochemistry Antibodies for Pathology

• 1. Liang YL, et al. Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. Nature. 2018 Sep;561(7724):492-497.
  2. Russell FA, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014 Oct;94(4):1099-142.