Calcitonin gene-related peptide 1

Also known as: Alpha-type CGRP, Calcitonin gene-related peptide I, CALCA, P06881

Calcitonin gene-related peptide 1 (CGRP1), also known as alpha-type CGRP, is a 37-amino-acid neuropeptide encoded by the *CALCA* gene. Its primary mechanism of action involves binding to a heterodimeric receptor complex composed of calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1). This interaction activates intracellular signaling cascades, including cyclic AMP (cAMP) elevation, leading to potent vasodilation of cerebral and peripheral blood vessels. CGRP1 is predominantly released from sensory nerve endings and plays a key role in neurogenic inflammation and nociception. Key research findings indicate that CGRP1 is a critical mediator in migraine pathophysiology. Elevated levels of CGRP1 have been detected during migraine attacks, and its infusion can trigger migraine-like headaches in susceptible individuals. Preclinical studies have demonstrated that CGRP1 contributes to vasodilation of meningeal arteries and sensitization of trigeminal nociceptive pathways. These findings have driven the development of CGRP1-targeted therapies, including monoclonal antibodies and small-molecule receptor antagonists, which have shown efficacy in migraine prophylaxis and acute treatment. Clinically, CGRP1 antagonism represents a validated therapeutic strategy for migraine management. Approved monoclonal antibodies (e.g., erenumab, galcanezumab) target either the CGRP ligand or its receptor, reducing migraine frequency and severity. However, CGRP1 remains classified as experimental in broader contexts, with ongoing research exploring its roles in other pain disorders, cardiovascular regulation, and inflammatory conditions. Its vasodilatory properties also raise considerations for potential cardiovascular effects in long-term use. For research purposes only — not medical advice.

Key data

Mechanism of action

CGRP1/CALCA is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex (PubMed:1318039, PubMed:33602864, PubMed:9620797). Dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role (PubMed:3492492). It also elevates platelet cAMP (PubMed:1318039). CGRP1 can also bind and activate CALCR-RAMP1 (AMYR1) receptor complex (PubMed:38603770)

Research & studies

Frequently asked questions

Related peptides