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Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25
Author(s) -
Hay Debbie L,
Garelja Michael L,
Poyner David R,
Walker Christopher S
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14075
Subject(s) - amylin , calcitonin gene related peptide , adrenomedullin , calcitonin receptor , calcitonin , receptor , pharmacology , chemistry , g protein coupled receptor , endocrinology , medicine , insulin , neuropeptide , islet
The calcitonin/CGRP family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two GPCRs, the calcitonin receptor (CTR) or the calcitonin receptor‐like receptor (CLR). Further diversity arises from heterodimerization of these GPCRs with one of three receptor activity‐modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM 1 and AM 2 receptors (CLR/RAMP2 or RAMP3) and the AMY 1, AMY 2 and AMY 3 receptors (CTR/RAMPs1–3 complexes, respectively). Apart from the CGRP receptor, there are only peptide antagonists widely available for these receptors, and these have limited selectivity, thus defining the function of each receptor in vivo remains challenging. Further challenges arise from the probable co‐expression of CTR with the CTR/RAMP complexes and species‐dependent splice variants of the CTR (CT (a) and CT (b) ). Furthermore, the AMY 1(a) receptor is activated equally well by both amylin and CGRP, and the preferred receptor for AM2/IMD has been unclear. However, there are clear therapeutic rationales for developing agents against the various receptors for these peptides. For example, many agents targeting the CGRP system are in clinical trials, and pramlintide, an amylin analogue, is an approved therapy for insulin‐requiring diabetes. This review provides an update on the pharmacology of the calcitonin family of peptides by members of the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology and colleagues.