- Nomenclature
- calcium sensing receptor
- Available assay modes
- Agonist, Inverse agonist, Antagonist, PAM, NAM
- Panels
- à la carte, Immunology/Infection, Oncology, Hematology, Endocrinology/Metabolism, Ophthalmology, Cardiology, Respiratory, Gastrointestinal, Dermatology, Musculoskeletal, Urology/Reproduction, Human non-orphan GPCRs
Calcium-sensing receptor
The calcium-sensing receptor (CaS) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [1]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [2,3], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [4,5,6,7,8]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [9,10]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [11] or decreased extracellular ionic strength [8]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.References
- Leach K, Sexton PM, Christopoulos A, et al. Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders. Br J Pharmacol 2014;171:1142-55.
- Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993;366:575-80.
- Quinn SJ, Ye CP, Diaz R, et al. The Ca2+-sensing receptor: a target for polyamines. Am J Physiol 1997;273:C1315-23.
- Conigrave AD, Quinn SJ, Brown EM. L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc Natl Acad Sci USA 2000;97:4814-9.
- Foord SM, Bonner TI, Neubig RR, et al. International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 2005;57:279-88.
- Ho C, Conner DA, Pollak MR, et al. A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat Genet 1995;11:389-94.
- Quinn SJ, Bai M, Brown EM. pH Sensing by the calcium-sensing receptor. J Biol Chem 2004;279:37241-9.
- Quinn SJ, Kifor O, Trivedi S, et al. Sodium and ionic strength sensing by the calcium receptor. J Biol Chem 1998;273:19579-86.
- Zhang C, Miller CL, Gorkhali R, et al. Molecular Basis of the Extracellular Ligands Mediated Signaling by the Calcium Sensing Receptor. Front Physiol 2016;7:441.
- Geng Y, Mosyak L, Kurinov I, et al. Structural mechanism of ligand activation in human calcium-sensing receptor. Elife 2016;5:.
- Campion KL, McCormick WD, Warwicker J, et al. Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism. J Am Soc Nephrol 2015;26:2163-71.
