Calcium-sensing receptor
- OMIM: 601199
- UniProt: P41180
- MGI: 1351351
The calcium- sensing receptor (English calcium sensing receptor ) is a receptor protein is selected from the group of G protein- coupled receptor that is responsible for the cell for the determination of extracellular calcium levels. The calcium- sensing receptor is particularly present on the surface of the main cells of the parathyroid and kidney tubule cells. It regulates the secretion of the parathyroid hormone, parathyroid hormone, and the reabsorption of calcium from the primary.
Mutations in the gene of the receptor that impair the function of (loss -of-function ), lead to familial hypokalzurischen hypercalcemia (FHH ) and neonatal severe primary hyperparathyroidism to. Mutations that increase the activity of the receptor (gain -of-function ) can contribute to autosomal dominant hypocalcemia with hypercalciuria lead (decreased serum calcium with increased excretion of calcium ).
Biosynthesis and protein structure
The gene for the calcium- sensing receptor is located on chromosome 3q21 CaSR and codes for a membrane-bound protein of 1059 amino acids with a large extracellular domain, seven transmembrane domains, and an intracellular appendix. The large extracellular domain consists of two lobes, which are responsible for the binding of the ligand and a cysteine - rich fraction. Upon binding of the ligand occurs at the cell surface to form dimers and the activation of phospholipase C, adenylate cyclase and protein kinase -dependent intracellular pathways.
Biological Function
In a decrease of the parathyroid gland extracellular calcium leads to an increase in PTH secretion. In the kidney, an increase of calcium to increased calcium excretion.
Pathology
In addition to the function of reducing and enhancing mutations to the receptor, there are other variations.
Variations (polymorphisms ) of the calcium receptor gene may thus lead to a reduced or increased calcium excretion and a predisposition to suffer from kidney stones, hypercalcemia or familial hypokalzurischer primary hyperparathyroidism.
Autoantibodies against the calcium- sensing receptor were observed in patients with increased serum calcium (hypercalcemia ) and reduced calcium excretion ( hypocalciuria ) found, in which no mutation was detectable and in patients with autoimmune hypoparathyroidism.
Pharmacology
The method used in the treatment of secondary hyperparathyroidism, cinacalcet leads as an allosteric modulator to an increase in the sensitivity of the calcium- sensing receptor for calcium.