Amylin receptor 2 (AMY2R) (AMY2R)

The Amylin receptor 2 (AMY2R) is a heterodimeric G protein-coupled receptor (GPCR) formed by the association of the calcitonin receptor (CTR) with the receptor activity-modifying protein 2 (RAMP2) [1, 6, 13]. As a member of the Class B GPCR family, it serves as a primary mediator for the physiological actions of amylin, a peptide hormone co-secreted with insulin from pancreatic beta cells [1, 11, 15]. Activation of AMY2R primarily stimulates the Gs-adenylyl cyclase pathway, increasing intracellular cyclic AMP (cAMP) levels to regulate glucose metabolism and energy balance [1, 13, 15]. Its biological roles include suppressing postprandial glucagon secretion, slowing gastric emptying, and promoting satiety through central nervous system signaling [2, 11, 15]. Consequently, AMY2R is a key therapeutic target for metabolic diseases such as type 2 diabetes and obesity, with drugs like the amylin analogue pramlintide and the dual agonist cagrilintide utilizing its pathways to improve glycemic control and induce weight loss [6, 12, 13]. Furthermore, the receptor is implicated in neurodegenerative conditions like Alzheimer's disease due to its ability to bind amyloid-beta peptides, suggesting potential roles beyond metabolic regulation [1, 14, 15].

Other names

AMY2AMY2 receptorCalcitonin receptor/RAMP2 complexCTR/RAMP2 heterodimer

Agonists bind to the AMY2R heterodimeric complex, activating Gs protein-mediated signaling which stimulates adenylyl cyclase to increase intracellular cyclic AMP (cAMP) levels, leading to the modulation of metabolic and neuroendocrine pathways.