Chapter 3 Calcium-Sensing Receptor and Associated Diseases

Geoffrey N. Hendy, Vito Guarnieri, Lucie Canaff

Research output: Contribution to journalArticlepeer-review

Abstract

The calcium-sensing receptor (CASR) is expressed in parathyroid hormone (PTH)-secreting cells of the parathyroid gland and cells lining the renal tubule. The activated CASR modulates intracellular signaling pathways altering PTH secretion and renal cation and water handling. Inherited abnormalities of the CASR gene give rise to a variety of disorders of mineral ion homeostasis. Heterozygous loss-of-function mutations cause familial (benign) hypocalciuric hypercalcemia (FHH) in which the lifelong mild hypercalcemia is generally asymptomatic. Homozygous inactivating mutations give rise to neonatal severe hyperparathyroidism (NSHPT) with extreme hypercalcemia and marked skeletal changes. Heterozygous activating mutations of the CASR cause autosomal dominant hypocalcemia (ADH) that may be asymptomatic or present with seizures in the neonatal period or childhood or later in life. Phenocopies of FHH or ADH are due to circulating CASR inactivating or activating autoantibodies, respectively. The CASR is the target of small molecule allosteric modifiers, either activators, calcimimetics, or inhibitors, calcilytics.

Original languageEnglish
Pages (from-to)31-95
Number of pages65
JournalProgress in Molecular Biology and Translational Science
Volume89
Issue numberC
DOIs
Publication statusPublished - 2009

Keywords

  • Allosteric modifiers
  • Autoimmunity
  • Autosomal dominant hypocalcemia
  • Calcilytics
  • Calcimimetics
  • Calcium-sensing receptor
  • Familial (benign) hypocalciuric hypercalcemia
  • Neonatal severe hyperparathyroidism
  • Parathyroid hormone

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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