The calcium-ion-sensing receptor

Conclusion The recent cloning, functional, morphologic, and genetic studies have established the CaSR as a vital component of the calcium homeostatic system. The CaSR provides both the sensing mechanism responsible for the regulation of parathyroid hormone secretion from parathyroid cells and the steep relationship between Ca²⁺ ₀ and urinary calcium excretion in the kidney. The renal CaSR appears to provide the crucial “sensing” mechanism in the thick ascending limb and papillary collecting duct for integrating and balancing salt, water, and divalent mineral loss. Direct interactions of extracellular Ca²⁺ with the renal CaSR could explain in large part the disordered water metabolism (ie, nephrogenic diabetes insipidus) observed under pathologic states of hypercalcemia (eg, with primary hyperparathyroidism or associated with certain malignancies). The promise of addition of new calcimimetic agents to our therapeutic arsenal is an exciting prospect. The CaSR story provides an nice example of going from bench to bedside. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology”, Tokyo, May 10, 1998.