Adrenomedullin receptors: pharmacological features and possible pathophysiological roles

Three receptor activity modifying proteins (RAMPs) chaperone calcitonin-like receptor (CLR) to the cell surface. RAMP2 enables CLR to form an adrenomedullin (AM)-specific receptor that is sensitive to AM-(22–52) (AM1 receptor). RAMP3 enables CLR to form an AM receptor sensitive to both calcitonin gene-related peptide (CGRP)-(8–37) and AM-(22–52) (AM2 receptor), though rat and mouse AM2 receptors show a clear preference for CGRPα-(8–37) over AM-(22–52). RAMP1 enables CRL to form the CGRP-(8–37)-sensitive CGRP1 receptor, which can also be activated by higher concentrations of AM. Here we review the available information on the pharmacological features and possible pathophysiological roles of the aforementioned AM receptors.