Molecular biology and clinical importance of the Ca(2+)-sensing receptor.
The Ca(2+)-sensing receptor (CaR) is a member of the seven-transmembrane domain, G protein-coupled receptor super-family. In the parathyroid gland, it mediates the inhibitory effects of extracellular Ca2+ on the secretion of parathyroid hormone. In the kidney, activation of the CaR causes decreased reabsorption of Ca2+ from the tubular lumen. Mutations in the CaR gene produce abnormalities of Ca2+ homeostasis. Heterozygous loss-of-function mutations cause familial hypocalciuric hypercalcemia. Homozygous loss-of-function mutations cause neonatal severe hyperparathyroidism. In contrast, gain-of-function CaR mutations result in autosomal dominant and sporadic hypoparathyroidism. The resulting hypoparathyroidism and hypocalcemia can range from asymptomatic to life-threatening. Patients with hypocalcemia due to CaR mutations also show disproportionate hypercalciuria that may increase the risk of nephrocalcinosis, nephrolithiasis, and renal insufficiency.
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1862, USA.
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De Luca
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Baron
D002118:Calcium / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics; D006961:Hyperparathyroidism / Q000235:genetics; D007668:Kidney / Q000502:physiology; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics*; D010280:Parathyroid Glands / Q000502:physiology; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium