Amylin 1 receptor (AMY1) (AMY1)

The Amylin 1 receptor (AMY1) is a functional heterodimeric G protein-coupled receptor complex formed by the association of the calcitonin receptor (CTR) and the receptor activity-modifying protein 1 (RAMP1) (IUPHAR/BPS Guide to PHARMACOLOGY, 2023). It serves as a high-affinity site for amylin, a peptide hormone co-secreted with insulin from pancreatic beta cells in response to nutrient intake (Lutz, T. A., 2010, Am J Physiol Regul Integr Comp Physiol). The AMY1 receptor is primarily expressed in the central nervous system, particularly in the area postrema of the hindbrain, where it mediates the satiating effects of amylin to regulate long-term energy balance (Boyle, C. N., & Lutz, T. A., 2014, Physiol Behav). Pharmacological activation of AMY1 leads to a reduction in postprandial glucagon secretion and a slowing of gastric emptying, which collectively prevent rapid spikes in blood glucose levels (Young, A., 2005, Adv Pharmacol). Consequently, AMY1 is a validated therapeutic target for metabolic diseases; pramlintide is an FDA-approved AMY1 agonist used for diabetes, while newer long-acting analogs like cagrilintide are being developed for chronic weight management (FDA Label for Symlin; Enebo, T., et al., 2021, The Lancet).

Other names

CTR/RAMP1 complexCalcitonin receptor/Receptor activity-modifying protein 1 complexAMY1 receptorAmylin receptor 1

Agonism of the AMY1 receptor complex leads to the activation of adenylate cyclase and increased intracellular cAMP, resulting in suppressed postprandial glucagon secretion, delayed gastric emptying, and centrally mediated induction of satiety.