Adrenomedullin 1 receptor (AM1 receptor) (AM1 receptor)

The Adrenomedullin 1 (AM1) receptor is a functional heterodimeric complex consisting of the Calcitonin Receptor-Like Receptor (CLR), a Class B G protein-coupled receptor, and the Receptor Activity-Modifying Protein 2 (RAMP2) [Source: IUPHAR]. This specific combination confers high affinity for the peptide hormone adrenomedullin (ADM), distinguishing it from the CGRP receptor and the AM2 receptor [Source: UniProt Q16602]. The AM1 receptor is widely expressed in the vascular endothelium and plays a pivotal role in cardiovascular homeostasis by mediating potent vasodilation, maintaining the endothelial barrier, and promoting angiogenesis [Source: PMID 30115606]. In clinical contexts, the AM1 receptor pathway is a target for treating circulatory shock and heart failure, where stabilizing vascular integrity and reducing systemic resistance are crucial [Source: PMID 29133777]. Conversely, in oncology, the receptor's role in tumor-associated angiogenesis makes it a potential target for inhibitory therapies to limit blood supply to malignant tissues [Source: PMID 19143332]. Therapeutic modulation of this receptor requires careful management to avoid adverse effects like severe hypotension or impaired tissue repair.

Other names

ADM1 receptorAdrenomedullin receptor type 1CLR/RAMP2 complexCALCRL/RAMP2

The AM1 receptor primarily couples to the Gs alpha subunit, which activates adenylate cyclase to increase intracellular cyclic adenosine monophosphate (cAMP) levels. This increase in cAMP activates protein kinase A (PKA) and the PI3K/Akt pathway, leading to the phosphorylation of endothelial nitric oxide synthase (eNOS) and subsequent vasodilation and endothelial cell survival [Source: PMID 30115606].