Adrenomedullin
Cardiovascular / VasoactiveAlso known as: ADM, AM, Adrenomedullin-52
Mechanism
Adrenomedullin is a 52-amino-acid peptide discovered in a pheochromocytoma tumor that turned out to be an important cardiovascular protector. It is a potent vasodilator, reduces blood pressure, protects the heart and kidneys, and has anti-inflammatory properties. Elevated adrenomedullin levels serve as a biomarker for sepsis severity and heart failure prognosis.
Technical detail
Adrenomedullin (ADM) is a 52-amino-acid peptide with a 6-residue ring structure (disulfide bond) and C-terminal amidation, structurally related to CGRP and amylin. It signals primarily through CLR (calcitonin receptor-like receptor) complexed with RAMP2 (forming the AM1 receptor) or RAMP3 (AM2 receptor), activating Gs-cAMP-PKA and PI3K-Akt-eNOS pathways for vasodilation. Also activates CREB-mediated cytoprotective gene expression. ADM is produced by endothelial cells, VSMCs, and cardiomyocytes. Functions include angiogenesis, lymphatic development, anti-apoptotic effects, and natriuresis. MR-proADM (stable precursor fragment) is used as a sepsis biomarker.
Evidence
- strong
Kita T et al. (2021) — J Gastroenterol — PMID: 33140199
Phase 2a randomized placebo-controlled trial in 28 steroid-resistant ulcerative colitis patients found the high-dose adrenomedullin arm achieved complete remission at 8 weeks in a small tracked subset, with only mild vasodilatory adverse events.
- emerging
Adrenomedullin Therapy in Patients with Refractory Ulcerative Colitis: A Case Series
Ashizuka S et al. (2016) — Dig Dis Sci — PMID: 26470867
Pilot case series in seven refractory ulcerative colitis patients found 14-day IV adrenomedullin improved disease activity in all patients, with mucosal healing/remission signals and no serious adverse effects.