CGRP-Beta

Cardiovascular / Migraine

Also known as: CGRP-beta, Beta-CGRP, CALCB, CGRP-II

Calcitonin/CGRP SuperfamilyResearch phase: Endogenous peptide (well characterized)Regulatory: Endogenous peptide. Anti-CGRP drugs (erenumab, fremanezumab, galcanezumab, gepants) target both CGRP isoforms for migraine.

Mechanism

CGRP-beta is the lesser-known sibling of CGRP-alpha (the peptide targeted by migraine drugs like erenumab and fremanezumab). Both forms are potent vasodilators, but beta-CGRP is encoded by a separate gene (CALCB vs. CALCA) and is predominantly expressed in the enteric nervous system rather than sensory neurons. It shares most of the same biological activities as alpha-CGRP.

Technical detail

CGRP-beta is a 37-amino-acid neuropeptide encoded by the CALCB gene (vs. CALCA for CGRP-alpha), differing by 3 amino acids in humans. It binds the same CLR/RAMP1 receptor complex as CGRP-alpha, activating Gs-cAMP-PKA signaling for vasodilation and Gq-PLC for additional cellular effects. CGRP-beta is predominantly expressed in enteric sensory neurons and the GI tract, while CGRP-alpha predominates in trigeminal ganglia (migraine-relevant). Both forms are equipotent vasodilators. Current anti-CGRP migraine therapeutics (monoclonal antibodies and gepants) do not fully distinguish between the two isoforms.

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