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Amylin receptor 3 (AMY3) is a heterodimeric G protein-coupled receptor formed by the association of the calcitonin receptor (CTR) and receptor activity-modifying protein 3 (RAMP3) (IUPHAR/BPS Guide to Pharmacology, 2023). It is one of three primary amylin receptor subtypes and is predominantly expressed in the brain, particularly in areas involved in appetite regulation such as the area postrema (PubMed: 29107052). AMY3 mediates the physiological actions of amylin, a hormone co-secreted with insulin, which includes the suppression of glucagon secretion, slowing of gastric emptying, and induction of satiety (Nature Reviews Drug Discovery, 2021). Due to its central role in energy balance and glucose metabolism, AMY3 is a major therapeutic target for the treatment of obesity and type 2 diabetes (Diabetes Care, 2022). Drugs like pramlintide and the long-acting analog cagrilintide target this receptor to achieve weight loss and improved glycemic control (The Lancet, 2021). Additionally, research suggests AMY3 may play a role in bone density regulation and the clearance of amyloid-beta in the brain (Journal of Biological Chemistry, 2017).
Agonism of the AMY3 receptor complex leads to the activation of intracellular signaling pathways, primarily via Gs proteins, resulting in increased cAMP production and subsequent physiological effects such as suppressed appetite and delayed gastric emptying (UniProt: P30988; O60896).
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