Amylin receptor 1 (AMY1R) (AMY1R)

The Amylin receptor AMY1R is a heterodimeric G protein-coupled receptor (GPCR) formed by the association of the calcitonin receptor (CTR) and the receptor activity-modifying protein 1 (RAMP1) [1, 2]. It belongs to the Class B GPCR family and is primarily involved in metabolic and neuroendocrine regulation [1, 3]. AMY1R is activated by the peptide hormone amylin, which is co-secreted with insulin from pancreatic beta cells, and it also shows high affinity for the calcitonin gene-related peptide (CGRP) [1, 7]. Upon activation, the receptor stimulates the Gs-protein pathway, increasing intracellular cAMP and triggering signaling cascades that reduce food intake, slow gastric emptying, and inhibit glucagon secretion [1, 5, 9]. In the context of disease, AMY1R is a significant therapeutic target for Type 2 diabetes and obesity, as its activation helps maintain glucose homeostasis and promote weight loss [2, 9, 11]. Additionally, due to its high affinity for CGRP, AMY1R is implicated in the pathophysiology of migraine and is a potential target for CGRP-related therapies [1, 7]. Emerging research also suggests a role for amylin receptors in Alzheimer's disease, where they may interact with amyloid-beta peptides [2, 4]. Drugs targeting this receptor include the FDA-approved amylin analog pramlintide and several long-acting agonists currently in clinical development, such as cagrilintide [2, 9, 11].

Other names

AMY1Amylin-1 receptorCTR/RAMP1 complexCalcitonin receptor/RAMP1 heterodimer

Agonists bind to the heterodimeric complex of the calcitonin receptor and RAMP1, inducing a conformational change that activates Gs-proteins. This leads to the stimulation of adenylyl cyclase and an increase in intracellular cAMP levels, which subsequently activates protein kinase A (PKA) and other downstream signaling pathways to regulate metabolic processes.