Calcium-sensing receptor

The calcium-sensing receptor (CaSR) is a Class C is_associated_with::G-protein coupled receptor which senses extracellular levels of is_associated_with::calcium ion. In the is_associated_with::parathyroid gland, the calcium-sensing receptor controls calcium is_associated_with::homeostasis by regulating the release of is_associated_with::parathyroid hormone (PTH).

Signal transduction
The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Increased calcium binding on the extracellular side gives a conformational change in the receptor, which, on the intracellular side, initiates the is_associated_with::phospholipase C pathway, presumably through a Gqα type of G protein, which ultimately increases intracellular concentration of calcium, which inhibits is_associated_with::vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some sources state) the is_associated_with::cAMP dependent pathway.

Pathology
Mutations that inactivate a CaSR gene cause is_associated_with::familial hypocalciuric hypercalcemia (FHH) (also known as familial benign hypercalcemia because it is generally asymptomatic and does not require treatment), when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia. Other mutations that activate CaSR are the cause of autosomal dominant is_associated_with::hypocalcemia or Type 5 is_associated_with::Bartter syndrome. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.

Therapeutic application
The drug is_associated_with::cinacalcet is an is_associated_with::allosteric modifier of the calcium-sensing receptor. It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.

is_associated_with::Calcilytic drugs which block CaSR, produce increased bone density in animal studies and have been researched for the treatment of is_associated_with::osteoporosis. Unfortunately clinical trial results in humans have proved disappointing, with sustained changes in bone density not observed despite the drug being well tolerated. More recent research has shown the CaSR receptor to be involved in numerous other conditions including is_associated_with::Alzheimer's disease, is_associated_with::asthma and some forms of is_associated_with::cancer,    and calcilytic drugs are being researched as potential treatments for these.

Interactions
Calcium-sensing receptor has been shown to interact with is_associated_with::Filamin.