[Calcium-sensing receptor and its related diseases]

The cloning of a G protein-coupled, extracellular calcium-sensing receptor (CaSR) provided direct evidence that Ca(2+)-sensing can occur through receptor-mediated activation of G proteins and their associated downstream regulators of cellular function. CaSR transcripts and protein are present in various tissues that are involved in Ca2+ homeostasis and that do not have well-established roles in Ca balance as well. The physiological relevance of the CaSR has been established by identifying inherited hyper-and hypocalcemia disorders resulting from CaSR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism result from inactivating CaSR mutations while autosomal dominant hypocalcemia is caused by activating mutations. CaSR may also play a role in water metabolism. Calcimimetics that activate CaSR are undergoing clinical trials and might prove effective in manipulation of serum calcium concentration and urinary calcium excretion through CaSR activities.