Calcium-sensing receptor and calcimimetic agents

• Type: Article in International Scientific Journal
• Date: 1999

Authors

Coburn, JW (Author) Other; Elangovan, L (Author) Other; Goodman, WG (Author) Other; João Frazão (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: Kidney International, Supplement

Vol. 56

Pages: S52-S58

ISSN: 0098-6577

Indexing

Scopus - 40 Citations

Other information

Authenticus ID: P-008-PTK

Abstract (EN): Recognizing the role of the extracellular calcium-sensing receptor (CaR) in mineral metabolism greatly improves our understanding of calcium homeostasis. The biology of the low affinity, G-protein-coupled CaR and the effects of its activation in various tissues are reviewed. Physiological roles include regulation of parathyroid hormone (PTH) secretion by small changes in ionized calcium (Ca2+) and control of urinary calcium excretion with small changes in blood Ca2+. The CaR also affects the renal handling of sodium, magnesium and water. Mutations affecting the CaR that make it either less or more sensitive to Ca2+ cause various clinical disorders; heterozygotes of mutations causing the CaR to be less sensitive to extracellular Ca2+ cause familial hypocalciuric hypercalcemia, while the homozygous form results in severe infantile hyperparathyroidism. Mutations causing increased sensitivity of the CaR to extracellular Ca2+ produce hereditary forms of hypoparathyroidism. Disorders, such as primary and secondary hyperparathyroidism, may exhibit acquired abnormalities of the CaR. Calcimimetic drugs, which amplify the sensitivity of the CaR to Ca2+, can suppress PTH levels, leading to a fall in blood Ca2+. Experiences with this agent in patients with secondary and primary hyperparathyroidism and parathyroid carcinoma are summarized. In animals and humans with hyperparathyroidism, this agent produces a dose-dependant fall in PTH and blood Ca2+, with larger doses causing more sustained effects. The treatment has been short-term except for one patient followed for more than 600 days for parathyroid carcinoma; nonetheless the drug did not cause major side- effects and appears to be safe. Further long-term controlled studies are needed with calcimimetic agents of this type.

Language: English

Type (Professor's evaluation): Scientific