Adrenomedullin receptor 1 (AM1)

Adrenomedullin receptor 1 (AM1) is a specialized class B G protein-coupled receptor complex formed by the heterodimerization of the calcitonin receptor-like receptor (CALCRL) and the receptor activity-modifying protein 2 (RAMP2) [1, 6]. It serves as the primary receptor for adrenomedullin (ADM), an endogenous peptide that plays a critical role in maintaining vascular and lymphatic homeostasis by promoting vasodilation, endothelial cell survival, and angiogenesis [2, 3]. AM1 signaling is essential for embryonic cardiovascular development and remains vital in adults for regulating blood pressure and protecting organs from oxidative stress and hypoxic injury [1, 6, 7]. In clinical contexts, the pathway is a significant therapeutic target; agonists are being explored for treating heart failure and sepsis to improve vascular stability, while antagonists are under investigation to block the pro-angiogenic signals that drive cancer progression and metastasis [9, 12, 15]. Despite its therapeutic potential, drug development is complicated by the high structural homology between AM1 and the related AM2 and CGRP receptors, which can lead to off-target effects and systemic hypotension [1, 11, 12]. Currently, biomarkers such as mid-regional pro-adrenomedullin (MR-proADM) are widely used in clinical settings to monitor the activity of this pathway as a prognostic indicator for organ failure and mortality risk [8, 14, 15].

Other names

AM1 receptorAM1RAdrenomedullin 1 receptorCALCRL/RAMP2 complexCLR/RAMP2 complexCalcitonin receptor-like receptor/Receptor activity-modifying protein 2 complex

Agonism (stimulating vasodilation and tissue repair) or Antagonism (inhibiting tumor angiogenesis and growth)