Amylin 3 receptor (AMY3R) (AMY3R)

The Amylin 3 receptor (AMY3R) is a heteromeric G protein-coupled receptor formed by the co-assembly of the calcitonin receptor (CTR) and the receptor activity-modifying protein 3 (RAMP3) [PMID: 10449444]. It serves as a high-affinity receptor for amylin, a peptide hormone co-secreted with insulin by pancreatic beta cells [PMID: 22474066]. AMY3R is primarily expressed in the hindbrain, specifically the area postrema, where it plays a critical role in regulating energy balance by inducing satiety and slowing gastric emptying [PMID: 30135113]. In addition to its role in appetite control, the receptor is involved in suppressing postprandial glucagon secretion and modulating bone resorption [PMID: 28414315]. Therapeutically, AMY3R is a major target for the treatment of obesity and type 2 diabetes [PMID: 33164165]. Drugs like cagrilintide and pramlintide act as agonists to mimic the effects of endogenous amylin, leading to significant weight loss and improved glycemic control [PMID: 34119211]. The receptor's signaling is primarily mediated through the Gs protein pathway, leading to increased intracellular cAMP [PMID: 10449444]. Recent clinical developments have focused on long-acting dual agonists that target both AMY3R and the calcitonin receptor to enhance weight loss efficacy [PMID: 33164165].

Other names

CTR/RAMP3 complexCalcitonin receptor/Receptor activity-modifying protein 3 complexAMY3Amylin receptor 3

Agonism of the AMY3R complex activates Gs-mediated signaling, increasing intracellular cAMP levels to modulate neuronal activity in the hindbrain, resulting in reduced food intake and delayed gastric emptying [PMID: 30135113].