Amylin receptor and Calcitonin receptor (AMYR and CTR)

The **Amylin receptor** is a heterodimeric cell surface protein formed by co-assembly of the **calcitonin receptor** (CTR) with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3), resulting in distinct subtypes: AMY1, AMY2, and AMY3[5][3]. These receptors belong to the **class B G protein-coupled receptor family** and are activated by the peptide hormone **amylin** (also known as islet amyloid polypeptide) as well as **calcitonin**, with varying affinity depending on the RAMP subtype. The amylin and calcitonin receptors play key roles in metabolic regulation, including **satiety signaling, inhibition of food intake, regulation of gastric emptying**, and modulation of **glucose homeostasis**[2][4][5]. They are **therapeutic targets for obesity and type 2 diabetes**, with FDA-approved **pramlintide** (an amylin mimetic) and investigational **dual amylin and calcitonin receptor agonists (DACRAs)** like **cagrilintide**[5]. Endogenous and exogenous ligands modulate signaling via distinct secondary structural changes and receptor complex dynamics[1][2][4]. Amylin receptor dysregulation has been implicated in metabolic and neurodegenerative conditions, such as obesity, diabetes, and Alzheimer’s disease[5]. The **calcitonin receptor** alone is a class B GPCR for calcitonin, primarily involved in calcium homeostasis, but it also forms the basis of functional amylin receptor complexes[5][6]. The pharmacology, selectivity, and functional responses of these receptors depend on the pairing of CTR with specific RAMPs, influencing their ligand binding and signaling profiles[3]. Overall, these receptors are of substantial current interest as multi-faceted metabolic and neurological therapeutic targets, with ongoing research seeking more selective agonists and a deeper understanding of their systemic effects[1][2][4][5].

Other names

AMY receptorAMYRCalcitonin receptor (CTR)Receptor activity-modifying protein complexes (AMY1 receptor, AMY2 receptor, AMY3 receptor)CT receptorCTR/RAMP1, CTR/RAMP2, CTR/RAMP3AMY1 receptorAMY2 receptorAMY3 receptorAMYRs

Agonism at the amylin receptor (mimics or potentiates native amylin action)[1][2][5] Dual agonism at amylin and calcitonin receptors (DACRA mechanism)[1][2][4] Modulation of glycemic control and appetite via activation of downstream G-protein signaling[3][6] Inhibition of glucagon secretion and slowing of gastric emptying