Abstract

Calcium-sensing receptor (CaSR), a member of family C of the G protein-coupled receptors, is expressed most abundantly in the parathyroid glands and kidney. It plays key role in these two organs because it senses changes in extracellular calcium and regulates PTH secretion and calcium reabsorption to suit the extracellular calcium concentration. In kidney, CaSR is expressed in all nephron segments. It has an inhibitory effect on the reabsorption of calcium, potassium, sodium and water, depending on the particular function of the different tubular tracts. Among its inhibitory effects, CaSR modulates the signaling pathways used by the tubulocytes to activate electrolyte or water reabsorption. The only site where there is no such inhibitory effect is in the proximal tubule, where CaSR enhances phosphate reabsorption to counteract the effect of PTH. CaSR mutations and polymorphisms cause disorders characterized by alterations in renal excretion and serum calcium concentrations. They also can cause sodium and potassium excretion disorders. CaSR also mediates the acute adverse renal effects of hypercalcemia, which include a reduced sodium, potassium and water reabsorption. From a teleological perspective, CaSR seems to protect human tissues against calcium excess in extracellular fluids.

Keywords: Gene, hypercalcemia, hypercalciuria, hypocalcemia, sodium handling, water reabsorption, renal stone