Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin₂ G protein-coupled receptor.

ABSTRACT: Adrenomedullin 2/intermedin (AM2/IMD), adrenomedullin (AM), and calcitonin gene-related peptide (CGRP) have functions in the cardiovascular, lymphatic, and nervous systems by activating three heterodimeric receptors comprising the class B GPCR CLR and a RAMP1, -2, or -3 modulatory subunit. CGRP and AM prefer the RAMP1 and RAMP2/3 complexes, respectively, whereas AM2/IMD is thought to be relatively nonselective. Accordingly, AM2/IMD exhibits overlapping actions with CGRP and AM, so the rationale for this third agonist for the CLR-RAMP complexes is unclear. Here, we report that AM2/IMD is kinetically selective for CLR-RAMP3, known as the AM₂R, and we define the structural basis for its distinct kinetics. In live cell biosensor assays, AM2/IMD-AM₂R elicited longer-durati

SUBMITTER: Babin KM 

PROVIDER: S-EPMC10248883 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature