Calcitonin receptor and Amylin receptors (CTR/AMY)

The Calcitonin receptor (CTR) is a Class B G protein-coupled receptor that serves as the primary mediator for the hormone calcitonin, playing a vital role in calcium homeostasis and bone remodeling by inhibiting osteoclast activity [1, 3]. A unique feature of CTR is its ability to form heterodimeric complexes with Receptor Activity-Modifying Proteins (RAMPs 1, 2, or 3), which shifts its ligand specificity to create Amylin receptors (AMY1, AMY2, and AMY3) [2, 4]. These amylin receptors are essential for metabolic regulation, as amylin—a peptide co-secreted with insulin—acts on the hindbrain to induce satiety, slow gastric emptying, and suppress glucagon release [2, 4]. In clinical practice, amylin analogs like pramlintide are utilized to improve glycemic control in patients with diabetes, while calcitonin is employed to treat osteoporosis and Paget's disease [3, 4]. Recent drug development has focused on long-acting amylin analogs and dual amylin and calcitonin receptor agonists (DACRAs) like cagrilintide for the treatment of obesity and type 2 diabetes [4]. These receptors are also being investigated for their potential roles in neuroprotection and cardiovascular health [2]. Targeting this system provides a multi-pronged approach to managing metabolic and skeletal disorders.

Other names

CALCRCTRAMY1AMY2AMY3Amylin receptor complexCT receptor

Agonism of the receptor complex leads to activation of intracellular signaling pathways (primarily Gs and Gq), resulting in suppressed glucagon secretion, delayed gastric emptying, and increased satiety for metabolic control, or inhibition of osteoclast activity for bone density preservation [2, 4].