[The key to the calcium regulation and calcium metabolism: G protein coupled membrane calcium receptor].
CALCIUM RECEPTOR: The calcium receptor can ìperceiveî small vanations in extracellular calcium concentrations and adapt cell response. The ìcalciostatî was hypothesized for several years before its discovery on parathyroid and other cells, particularly renal cells. It can couple with protein G and has 7 transmembrane domains.
The calcium receptor is stimulated by increased extracellular calcium level which, via a GDP/GTP exchange by the heterotrimeric protein G and a transduction network, triggers release of intracellular calcium ion stores and influx of extracellular calcium ions through the cationic channels. A FUNDAMENTAL ROLE: The calcium receptor controls not only parathormone and thyrocalcitonin secretion, but also plays an important role in calcium transfer from the mother to fetus, in reabsorption of calcium by the large ascending cortial portion of the Henlé loop, and in reabsorption of water by the collecting tubes. DISEASE STATES: Mutations affecting the calcium receptor sequence cause hereditary or familial parathyroid diseases. In addition, decreased expression of the calcium receptor protein and signal has been demonstrated in primary hyperparathyroidism as well as in secondary hyperparathyroidism. The calcium receptor is also expressed in a large variety of tissues and could be implication in other disease states.
Medical treatment of primary hyperparathyroidism using specific calcium receptor agonists derived from phenylalkylamines is now possible. The efficacy of these drugs should be demonstrated in the treatment of secondary hyperparathyroidism and chronic renal failure. Other therapeutic implications are possible.
Hory
B
B
Médecin des hôpitaux, Avignon. horybgj@aol.com
D000818:Animals; D002116:Calcitonin / Q000502:physiology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006961:Hyperparathyroidism / Q000503:physiopathology / Q000628:therapy; D010281:Parathyroid Hormone / Q000502:physiology; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000502:physiology*
D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002116:Calcitonin; D019204:GTP-Binding Proteins; D002118:Calcium