title: A cloned Ca(2+)-sensing receptor: a mediator of direct effects of extracellular Ca2+ on renal function?
abstract: Changes in the extracellular calcium concentration [Ca2+]o modulate several aspects of renal function through unknown mechanism(s). cDNA encoding a Ca2+o-sensing receptor from bovine parathyroid and rat kidney that appears to mediate several of the known effects of Ca2+o on parathyroid and renal function were recently isolated. The expressed receptor activates phospholipase C, showing a pharmacologic profile very similar to that of the native receptor. Its deduced amino acid sequence identifies it as a member of the superfamily of G protein-coupled receptors. The physiologic relevance of the receptor has been established by the demonstration that mutations in it cause three inherited diseases of calcium metabolism. Two hypercalcemic disorders, familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, result from inactivating mutations when present in the heterozygous and homozygous states, respectively. An activating mutation, in contrast, causes an autosomal dominant form of hypocalcemia. In the kidney, the receptor is expressed most abundantly in the thick ascending limb, where it likely modulates sodium chloride, calcium, and magnesium reabsorption and, perhaps, urinary concentrating ability. Studies are currently underway to determine whether it also mediates the effects of Ca2+o on other parameters of kidney function, such as RBF, glomerular filtration, renin secretion, and vitamin D metabolism. Thus, this Ca2+o-sensing receptor permits extracellular calcium ions to act not only as an intracellular second messenger but also in a "hormone-like" role as an extracellular first messenger.
authors: Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: E M
authors: EM
authors: Brown
authors: S C
authors: SC
authors: Hebert
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*
chemical_list: D002118:Calcium