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.
De Luca
F
F
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1862, USA.
Baron
J
J
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