College Papers

The calcium-sensing receptor

The calcium-sensing receptor (CaSR) plays an important role in the process of maintenance of the extracellular ionized calcium concentration (Ca2+o), mainly by modulating the function of chief cells in the parathyroid gland. CaSR enables the parathyroid glands as well as other CaSR-expressing cells involved in calcium homeostasis (the kidneys and bone), to sense alterations in the level of Ca2+o and to respond with changes in function that are aimed at regulating normal blood calcium concentration. Numerous pathologies are associated with Ca2+o sensing that reset the serum calcium concentration upwards or downwards. For instance, geterogygous inactivating mutations of the CaSR result in a benign form of hypercalcaemia (also called familial hypocalciuric hypercalcaemia), whereas homozygous mutations of the CaSR result in much more severe hypercalcaemic disorder occurring from marked hyperparathyroidism (or neonatal severe hyperparathyroidism). Activating mutations cause a hypocalcaemic syndrome of varying severity, termed ‘autosomal-dominant hypocalcaemia or hypoparathyroidism’ as well as Bartter’s syndrome type V. Calcimimetic CaSR activators and calcilytic CaSR antagonists have also been developed with potential for use in the treatment of these disorders.