Calcitonin Receptor Antibodies

The calcitonin receptor family is built around two class B1 G protein-coupled receptors, the calcitonin receptor (CTR, encoded by CALCR) and the calcitonin receptor-like receptor (CLR, encoded by CALCRL). CTR responds to calcitonin on its own and forms the three amylin receptor subtypes AMY₁–AMY₃ when paired with receptor activity-modifying proteins RAMP1–RAMP3, respectively. CLR associates with RAMP1 to form the canonical calcitonin gene-related peptide (CGRP) receptor and with RAMP2 or RAMP3 to form the adrenomedullin receptors AM₁ and AM₂, respectively. These receptor complexes signal predominantly through Gs to increase intracellular cAMP, although coupling can vary with the ligand and cellular context. CTR is expressed in osteoclasts, where calcitonin inhibits bone resorption, while central amylin receptors participate in the control of food intake. CGRP and adrenomedullin receptors are expressed in the vasculature and regulate vascular tone, and CGRP signaling in the trigeminovascular system contributes to migraine. RAMP association influences cell-surface expression and ligand selectivity and can also affect receptor internalization and recycling. Clinically used agonists include salmon calcitonin for selected disorders of bone and calcium metabolism and the amylin analogue pramlintide as an adjunct to mealtime insulin. The receptor-directed antibody erenumab and small-molecule CGRP receptor antagonists such as rimegepant are approved for migraine treatment or prevention, depending on the agent.