Adrenomedullin receptor complex (AM receptor)

The Adrenomedullin receptor complex is a heterodimeric G protein-coupled receptor (GPCR) system essential for cardiovascular and lymphatic homeostasis. It is formed by the association of the Calcitonin receptor-like receptor (CLR, also known as CALCRL) with one of two Receptor activity-modifying proteins: RAMP2 (forming the AM1 receptor) or RAMP3 (forming the AM2 receptor). These complexes primarily mediate the physiological effects of the peptide hormone adrenomedullin, leading to potent vasodilation, regulation of vascular permeability, and stimulation of angiogenesis. In clinical contexts, the AM receptor system is a significant therapeutic target for treating heart failure and sepsis, where modulating vascular tone and endothelial barrier function is critical for patient survival. Conversely, in oncology, inhibiting the AM receptor pathway is explored as a strategy to suppress tumor-induced angiogenesis and lymphangiogenesis. The specificity of the receptor for adrenomedullin over other calcitonin family peptides is strictly determined by the specific RAMP subunit present in the complex. (Sources: UniProt Q16602, O60895; IUPHAR Guide to Pharmacology; PMID: 29453914, 30135115).

Other names

AM1 receptorAM2 receptorAdrenomedullin receptor 1Adrenomedullin receptor 2CALCRL/RAMP2 complexCALCRL/RAMP3 complexCLR/RAMP2CLR/RAMP3

Agonism of the Adrenomedullin receptor complex activates the Gs protein-coupled signaling pathway, leading to increased intracellular cyclic adenosine monophosphate (cAMP) levels and activation of protein kinase A (PKA) and the PI3K/Akt pathway, which promotes smooth muscle relaxation and endothelial cell survival. Antagonism of the complex blocks these pathways to inhibit pathological angiogenesis or vascular leakage.