Amylin receptor AMY1 (AMY1)

The Amylin receptor AMY1 is a heterodimeric G protein-coupled receptor (GPCR) formed by the association of the calcitonin receptor (CTR) and the receptor activity-modifying protein 1 (RAMP1) [1, 2]. It serves as a critical component of the gut-brain axis, primarily located in the area postrema of the hindbrain and the hypothalamus, where it mediates the physiological effects of amylin, a peptide hormone co-secreted with insulin [5, 10]. Activation of AMY1 promotes meal-ending satiety, slows gastric emptying, and suppresses postprandial glucagon secretion, thereby playing a vital role in glucose homeostasis and energy balance [7, 8]. Due to its high affinity for both amylin and calcitonin gene-related peptide (CGRP), AMY1 is also implicated in neurovascular functions such as vasodilation and migraine pathogenesis [2, 3]. Therapeutically, AMY1 is a major target for metabolic disorders, with the amylin analog pramlintide currently approved for the treatment of type 1 and type 2 diabetes [1, 7]. Newer long-acting agonists like cagrilintide and dual-agonists like amycretin are under intensive clinical development for the management of obesity, often showing synergistic effects when combined with GLP-1 receptor agonists [11, 12, 14]. Beyond metabolism, the receptor is being investigated for its potential role in neurodegenerative conditions like Alzheimer's disease, where amylin signaling may influence amyloid-beta clearance and neuroprotection [6, 9]. Common safety concerns associated with AMY1-targeting drugs include dose-dependent gastrointestinal side effects such as nausea and vomiting [12, 14].

Other names

AMY1RCalcitonin receptor/RAMP1 complexCTR/RAMP1 heterodimerAmylin receptor 1

Agonists bind to the heterodimeric AMY1 receptor complex, triggering Gs-protein-mediated activation of adenylyl cyclase and increasing intracellular cAMP levels to modulate metabolic and satiety pathways [2, 3, 13].