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The calcium-sensing receptor in human disease
Jacob Tfelt-Hansen1, Peter Schwarz, Edward M Brown
1Endocrine-Hypertension Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical school, 221 longwood avenue, LMRC room 205, Boston, MA 02115, USA. jtfelt@rics.bwh.harvard.edu
Frontiers in Bioscience : a Journal and Virtual Library
|April 18, 2003
Summary
The calcium-sensing receptor (CaR) regulates calcium levels by controlling parathyroid hormone secretion. Mutations and autoantibodies affecting CaR cause calcium disorders, while calcimimetics offer therapeutic potential.
Area of Science:
- Endocrinology
- Molecular Biology
- Nephrology
Background:
- The calcium-sensing receptor (CaR), a G protein-coupled receptor, is crucial for maintaining systemic calcium homeostasis.
- CaR is located on parathyroid gland chief cells, sensing extracellular calcium (Ca2+) and regulating parathyroid hormone (PTH) secretion.
- Intracellular signaling pathways linked to CaR include phospholipase C (PLC) and mitogen-activated protein kinases.
Purpose of the Study:
- To elucidate the pivotal roles of CaR in systemic calcium homeostasis.
- To investigate the impact of CaR mutations on calcium balance and related disorders.
- To explore the therapeutic potential of targeting CaR.
Main Methods:
- Discovery and characterization of the calcium-sensing receptor (CaR).
- Analysis of functionally important mutations in the CaR gene.
- Investigation of circulating autoantibodies to CaR in human patients.
- Evaluation of calcimimetic drugs in preclinical models.
Main Results:
- CaR mutations altering PTH secretion set points and renal calcium excretion cause hypercalcemia (inactivation) or hypocalcemia (activation).
- Circulating autoantibodies to CaR mimic clinical presentations of CaR mutation-induced diseases.
- Calcimimetics demonstrate promise for treating conditions like renal secondary hyperparathyroidism.
Conclusions:
- The CaR plays a vital role in calcium homeostasis, with implications for various physiological processes.
- CaR dysfunction, through mutations or autoantibodies, leads to significant calcium-related disorders.
- Targeting CaR with drugs like calcimimetics represents a promising therapeutic strategy for specific conditions.