MINIREVIEW Agonists and Allosteric Modulators of the Calcium-Sensing Receptor and Their Therapeutic Applications

The calcium-sensing receptor (CaR) belongs to the G protein-coupled receptor superfamily, with a characteristic structure consisting of seven transmembrane helices, an intracellular C-terminal and an extracellular N terminal domain. The primary physiological function of the CaR is the maintenance of con-stant blood Ca2 levels, as a result of its ability to sense very small changes in extracellular Ca2 (Ca2o). Nevertheless, in addition to being expressed in tissues involved in Ca2o ho-meostasis, the CaR is also expressed in tissues not involved in mineral homeostasis, suggestive of additional physiological functions. Numerous agonists and modulators of the CaR are now known in addition to Ca2o, including various divalent and trivalent cations, aromatic L-amino acids, polyamines, and ami-noglycoside antibiotics. The signaling of the CaR is also regu