Function of CASR

Function of CASR

In the chief cells of the parathyroid glands, binding of calcium to CASR activates a trimeric GTP-binding protein (G protein) in contact with the cytoplasmic face of the CASR transmembrane molecule. The activated G protein stimulates the membrane-bound enzyme phospholipase C to generate inositol-1,4,5-triphosphate from a phospholipid component of the plasma membrane. Inositol-1,4,5- triphosphate then triggers release of calcium from internal storage vesicles, leading to an increase in the cytosolic calcium concentration. CASR probably also interacts with a type of G protein that causes inhibition of adenylate cyclase, coupling CASR activation to the cAMP second messenger system (4). Ultimately, binding of extracellular calcium to CASR leads to inhibition of parathyroid hormone secretion from the chief cells.

In the kidneys, CASR is expressed in the cells lining the distal part of the kidney tubules There, calcium reabsorption occurs through the paracellular route, driven by a small positive charge of the tubular lumen relative to the interstitial fluid. This small positive charge depends on active sodium-potassium-chloride reabsorption, which is accompanied by some potassium backflow. Binding of calcium to CASR inhibits active sodium-potassium-chloride reabsorption and thus also calcium reabsorption.

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