Adrenomedullin receptor type 1 (AM1 receptor)

The Adrenomedullin receptor type 1 (AM1 receptor) is a specialized heterodimeric G protein-coupled receptor (GPCR) formed by the association of the Calcitonin receptor-like receptor (CALCRL) and the Receptor activity-modifying protein 2 (RAMP2). This specific pairing determines the receptor's high affinity for the potent vasodilator peptide adrenomedullin (AM). The AM1 receptor plays a critical role in maintaining vascular integrity, regulating blood pressure, and promoting the development of new blood vessels. In clinical settings, the AM1 system is a key target for treating septic shock and heart failure, where stabilizing vascular barrier function is paramount. Conversely, because the receptor facilitates tumor angiogenesis and lymphangiogenesis, it is also investigated as a target for anti-cancer therapies. Current pharmacological approaches include the use of monoclonal antibodies like Adrecizumab to modulate ligand bioavailability and peptide antagonists for experimental oncology research.

Other names

AM1RAdrenomedullin 1 receptorCALCRL/RAMP2 complexCLR/RAMP2 receptor complex

The receptor primarily functions through Gs protein coupling, leading to the activation of adenylate cyclase and increased intracellular cAMP levels. It can also activate the PI3K/Akt and MAPK pathways to promote cell survival and angiogenesis. Therapeutic modulation involves agonizing the receptor for cardiovascular protection or using antibodies to stabilize the ligand (e.g., Adrecizumab) to improve vascular barrier function in sepsis.