Calcitonin Gene-Related Peptide
37-amino acid neuropeptide potent vasodilator involved in migraine pathophysiology and pain signaling.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C163H265N51O50S2 |
| Molecular Weight | 3790 Da |
| Peptide Class | Neuropeptide (37 amino acids) |
| Disulfide Bonds | 1 (Cys2-Cys7) |
| Forms | alpha-CGRP, beta-CGRP |
| Receptor | CLR/RAMP1 (CGRP receptor) |
Structure
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide with a single disulfide bond between Cys2 and Cys7 and a C-terminal amidation. Two forms exist: alpha-CGRP (from CALC1 gene, sensory neurons) and beta-CGRP (from CALC2 gene, enteric neurons). Both forms share the same receptor.
Mechanism of Action
CGRP binds the CGRP receptor (CLR/RAMP1 complex), activating adenylyl cyclase and increasing cAMP. This causes potent vasodilation (most potent endogenous vasodilator), promotes neurogenic inflammation, sensitizes nociceptors, and contributes to migraine pathophysiology through trigeminovascular activation.
Clinical Applications
- Migraine: CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and gepants
- Cluster headache: CGRP-targeted therapies
- Cardiovascular: Endogenous vasodilator and cardioprotectant
- Pain: Peripheral and central pain sensitization
- Bone: Osteoblast stimulation
Pharmacology
- Half-life: 6-10 minutes (native), days-weeks (monoclonal antibodies)
- Potency: 10x more potent than adrenomedullin as vasodilator
- Release: Trigeminal nerve endings during migraine
- Alpha vs beta: 94% sequence identity
References
- Rosenfeld, M.G., et al. (1983). Production of a novel neuropeptide by calcitonin gene expression. Nature, 304, 129-135.
- Edvinsson, L., et al. (2018). CGRP receptor antagonists and antibodies for migraine. Nature Reviews Neurology, 14, 338-350.
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