Calcitonin receptor (CTR) (CTR)

The calcitonin receptor (CTR) is a high-affinity G protein-coupled receptor (GPCR) belonging to the Class B family, primarily expressed on the surface of osteoclasts and in certain regions of the brain and kidney [1, 3]. In rats, its primary biological role is the maintenance of calcium homeostasis by inhibiting bone resorption through the direct suppression of osteoclast activity and promoting renal calcium excretion [1, 4]. Upon binding its ligand, calcitonin, the receptor triggers intracellular signaling pathways involving adenylate cyclase and phospholipase C, leading to a rapid reduction in blood calcium levels [3, 4]. The receptor can also form heterodimers with receptor activity-modifying proteins (RAMPs) to function as amylin receptors, expanding its physiological influence to glucose metabolism and satiety [3]. Therapeutically, the CTR is a major target for treating metabolic bone diseases such as osteoporosis and Paget's disease, where excessive bone loss occurs [5]. While salmon calcitonin is a potent agonist used clinically, long-term efficacy can be limited by receptor desensitization, a phenomenon known as tachyphylaxis [5]. Preclinical studies using the rat calcitonin receptor have been essential for characterizing the pharmacology of calcitonin analogs and understanding the skeletal-renal axis [2, 4]. Safety concerns associated with CTR-targeting drugs include potential increased risks of malignancy with chronic use and transient hypocalcemia [5]. Sources: [1] UniProt Consortium. UniProtKB - P25114 (CALCR_RAT). https://www.uniprot.org/uniprotkb/P25114/entry [2] National Center for Biotechnology Information (NCBI). Gene ID: 24244, Calcr (Rattus norvegicus). https://www.ncbi.nlm.nih.gov/gene/24244 [3] IUPHAR/BPS Guide to PHARMACOLOGY. Calcitonin receptors. https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=11 [4] Lin HY, et al. Expression cloning of an adenylate cyclase-coupled calcitonin receptor. Science. 1991;254(5034):1022-1024. doi:10.1126/science.1314130 [5] U.S. Food and Drug Administration (FDA). Miacalcin (calcitonin-salmon) Injection Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017769s035s036lbl.pdf

Other names

CALCRCT-RCalcitonin receptor type 1

Agonist activation of the receptor leads to increased intracellular cAMP and calcium levels, which inhibits the resorptive activity of osteoclasts.