The calcitonin peptide family comprises calcitonin, amylin, calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and intermedin (AM2). Calcitonin is a 32 amino acid peptide, involved in bone homeostasis (Sexton PM et al, 1999). Amylin is a product of the islet beta-cell (Cooper GJ et al, 1987), along with insulin and probably has a hormonal role in the regulation of nutrient intake (Young A and Denaro M, 1998). Adrenomedullin (AM) is a ubiquitously expressed peptide initially isolated from phaechromocytoma (a tumour of the adrenal medulla) (Kitamura K et al, 1993). Both AM and AM2 (Takei Y et al, 2004) belong to a family of calcitonin-related peptide hormones important for regulating diverse physiologic functions and the chemical composition of fluids and tissues.
The receptor family for these peptides consists of two class B GPCRs, the calcitonin receptor (CT) and calcitonin receptor-like receptor (CL) (Poyner DR er al, 2002). Whilst the receptor for calcitonin is a conventional class B GPCR, the receptors for CGRP, AM and amylin require additional proteins, called the receptor activity modifying proteins (RAMPs). There are three RAMPs in mammals; they interact with the CT receptor to convert it to receptors for amylin. For CGRP and AM, the related CL interacts with RAMP1 to give a CGRP receptor and RAMP2 or 3 to give AM receptors. CL by itself will bind no known endogenous ligand.