Adrenomedullin selectivity of calcitonin-like receptor/receptor activity modifying proteins

Co-expression of an initially orphan calcitonin receptor-like (CL)1 receptor with individual receptor-activity-modifying proteins (RAMP)1, -2 and -3 results in CL receptor/RAMP1, -2 and -3 proteins at the cell surface. The RAMP define the selectivity of the CL receptor for the vasodilatory peptides adrenomedullin (AM) and calcitonin gene-related peptide (CGRP). The selectivity for AM and CGRP agonists and antagonists of human, rat, porcine and bovine CL receptors, co-expressed with RAMP2 and -3, has been studied in different cell types. This revealed CL receptor/RAMP2 and CL receptor/RAMP3 as AM1 and AM2 receptor subtypes, respectively. The AM1 receptor crossreacts with CGRP at high and the AM2 receptor at lower concentrations. Here the pharmacological properties of the cloned AM receptors are compared to those revealed in tissues and cell lines. According to nomenclature recommendation of the IUPHAR (International Union of Pharmacology) subcommittee XXXII, the former CRLR is now the CL receptor (1).