Amylin

Abstract

Amylin is a 37 amino acid peptide hormone that is closely related to calcitonin gene-related peptide (CGRP). Amylin and CGRP share a receptor and are reported to have several similar biological actions. Given the important role of CGRP in migraine and intense efforts to develop drugs against this target, it is important to consider potential areas of overlap between the amylin and CGRP systems. This short review provides a brief introduction to amylin biology, the use of an amylin analog to treat diabetes, and consideration of whether amylin could have any role in headache disorders. Finally, this review informs readers about the AMY 1 (amylin subtype 1) receptor, which is a dual receptor for amylin and CGRP and potentially plays a role in the bioactivity of both of these peptides.

Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

“…It is noteworthy that CGRP is a potent agonist at the CGRP receptor that is made up of CLR with RAMP1, and also the AMY1 receptor that is made up of CTR with RAMP1 . The converse is not, however, true, as amylin is only a weak activator of the CGRP receptor …”

“…Agonist and CGRP modulator pharmacology at CGRP and amylin receptors (adapted from Hay). 1: CGRP peptide neutralizing antibody; 2: CGRP receptor blocking antibody; 3: CGRP small molecule receptor antagonist.…”

“…9 The converse is not, however, true, as amylin is only a weak activator of the CGRP receptor. 10,11 The mechanism of CGRP binding to its receptor is thought to be represented by a 2-domain model. In this model, the C-terminal region of CGRP first binds with high affinity to the extracellular N-terminal regions of CLR and RAMP1 forming an affinity trap that increases the local concentrations of CGRP to allow the N-terminal of CGRP to interact with the juxta-membrane region of CLR and trigger the accumulation of cAMP.…”

CGRP, Amylin, Immunology, and Headache Medicine

“…Characteristics which unite this family are positioning of a disulfide bond and an amidated C terminus. 32 αCGRP is encoded on chromosome 11p15.2 by the calcitonin polypeptide alpha (CALCA) gene, which by alternative or differential splicing also encodes calcitonin in a tissue-specific manner and pro-calcitonin, katacalcin, and N/C-terminal peptides from pro-CGRP. [29][30][31] Similarity over their 3′ coding regions is also high for a carboxyl-terminal amide (NH 2 ) residue.…”

“…12,43 αCGRP is preferentially expressed in sensory neurons where its concentration is 3-to nearly 7-fold higher than that of βCGRP. 32 Amylin serum half-life in rats is approximately 13 minutes. 44,45 Whereas CGRP isoforms bind to several family receptors including amylin's, amylin does not bind with high affinity for the CGRP receptor or any similar complex.…”