Calcitonin receptor-receptor activity-modifying protein complex (AMY receptor)

The Calcitonin receptor-receptor activity-modifying protein (RAMP) complex, commonly referred to as the Amylin receptor (AMY receptor), is a heterodimeric G protein-coupled receptor (GPCR) essential for metabolic regulation (PubMed: 29661863). This complex is formed by the association of the Calcitonin receptor (CTR) with one of three accessory proteins: RAMP1, RAMP2, or RAMP3, which modify the receptor's ligand specificity to favor the peptide hormone amylin (UniProt: P30988, O60894). Amylin is co-secreted with insulin from pancreatic beta cells and acts on these receptors in the brain to regulate glucose homeostasis by slowing gastric emptying, suppressing glucagon secretion, and promoting satiety (NIH: PMC6349286). Beyond metabolic roles, the CTR/RAMP1 complex (AMY1) also functions as a high-affinity receptor for calcitonin gene-related peptide (CGRP), involving it in vasodilation and pain transmission (Guide to Pharmacology). Pharmacological targeting of these complexes, such as with the amylin analog pramlintide or the dual agonist cagrilintide, provides a potent mechanism for managing type 2 diabetes and obesity (PubMed: 33887214). However, therapeutic use is often limited by gastrointestinal side effects like nausea and vomiting.

Other names

Amylin receptorAMY1 receptorAMY2 receptorAMY3 receptorCTR-RAMP complexCalcitonin receptor-RAMP complex

Agonism of the heterodimeric receptor complex leading to increased cyclic AMP (cAMP) production, which mediates physiological effects such as suppression of postprandial glucagon secretion, slowing of gastric emptying, and promotion of satiety.